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Leonard J, Kepplinger D, Torres E, Hu CH, Veneziano R, Hoemann CD. Comparative analysis of Lox-1 and CD36 expression in human platelets and on circulating microparticles during ARDS-induced coagulopathy. Thromb Res 2024; 244:109202. [PMID: 39546984 DOI: 10.1016/j.thromres.2024.109202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/02/2024] [Accepted: 10/28/2024] [Indexed: 11/17/2024]
Abstract
INTRODUCTION Acute respiratory distress syndrome (ARDS) patients are at risk of thrombosis through mechanisms implicating oxidized low-density lipoprotein (oxLDL). Endothelial cells, immune cells and platelets were reported to express scavenger receptors for oxLDL: Lox-1 and CD36. We hypothesized that platelets shed a soluble Lox-1 ectodomain (sLox-1) and release CD36-bearing procoagulant microparticles (MPs), that both become elevated in subjects with ARDS-induced coagulopathy. METHODS Using anti-extracellular and anti-intracellular Lox-1 antibodies, we first tested by western blot whether platelets express Lox-1 and shed sLox-1 upon activation. Next, we measured sLox-1 in blood plasma of 23 healthy donors and 48 ARDS Omega patients with and without coagulopathy, and assessed the corresponding MP fraction for Lox-1/sLox-1 and CD36. We evaluated mechanisms of sLox-1-MP association. Recombinant proteins were used as controls. RESULTS Resting platelets expressed abundant CD36 (7.8 ng/μg protein extract) which was released upon oxLDL stimulation, but undetectable levels of full-length 37 kDa Lox-1 receptor or 24 kDa sLox-1 (below 10 pg/μg). In an RNAseq meta-analysis, platelets expressed negligible OLR1, the mRNA encoding Lox-1, compared to CD36. A subset of ARDS patients showed elevated plasma sLox-1 and MP-associated sLox-1 compared to healthy controls that was positively associated with 90-day survival and low coagulopathy. MP-associated CD36 was reduced in ARDS plasma compared to healthy donors and did not correlate with survival, coagulopathy, or sLox-1. oxLDL promoted sLox-1 binding to CD36-deficient MPs. CONCLUSION sLox-1 arising from a non-platelet cell source associates with circulating MPs which could serve a protective role in ARDS.
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Affiliation(s)
- Julia Leonard
- Department of Bioengineering, College of Engineering and Computing, George Mason University, Manassas, VA 20110, United States of America
| | - David Kepplinger
- Department of Statistics, College of Engineering and Computing, George Mason University, Fairfax, VA 22030, United States of America
| | - Elmer Torres
- Department of Bioengineering, College of Engineering and Computing, George Mason University, Manassas, VA 20110, United States of America
| | - Chih-Hsiang Hu
- Department of Bioengineering, College of Engineering and Computing, George Mason University, Manassas, VA 20110, United States of America
| | - Remi Veneziano
- Department of Bioengineering, College of Engineering and Computing, George Mason University, Manassas, VA 20110, United States of America
| | - Caroline D Hoemann
- Department of Bioengineering, College of Engineering and Computing, George Mason University, Manassas, VA 20110, United States of America.
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Kanuri SH, Sirrkay PJ. Profiling of microglial-originated microvesicles to unearthing their lurking potential as potent foreseeable biomarkers for the diagnosis of Alzheimer's disease: A systematic review. Brain Circ 2024; 10:193-204. [PMID: 39526104 PMCID: PMC11542763 DOI: 10.4103/bc.bc_113_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 04/02/2024] [Accepted: 04/16/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Alzheimer's Disease is a neurodegenerative disease characterized by accumulation of phosphorylated tau and amyloid deposits within the brain tissues in the elderly population. Numerous studies established that amassment of these toxic accretions within the brain tissues initiates neuronal demise and synaptic impairment which becomes the underlying basis for memory loss and cognitive abnormalities in these patients. HYPOTHESIS Hypoxia, oxidative stress, and inflammation are commonly encountered perils in the neuronal milieu that derail the neuron-synapse interactions and maneuver them to undergo apoptosis. A spinoff from neuronal desecration is microglial activation which forms a cardinal role in mounting innate immune defenses for warding off and reversing off toxic stimulus encountered. RESULTS A potential ramification of microglial activation in this context is assembly, processing and exuding of micro-vesicles into the extracellular space. These micro-vesicles will be packaged with amyloid and tau deposits which accumulate intracellularly within microglial cells secondary to their professional scavenging function. These microglial MVs are prone to seed tau and amyloid beta into the surrounding neuron-synapse framework, thus are implicated in spreading the disease pathology in AD. CONCLUSIONS Therefore, these MVs can be considered as an omen for disease initiation, progression, monitoring as well gauging the treatment response in the clinical AD cohorts. We speculate future research studies to unmask the dormant potential of these microglial MVs as reliable markers for diagnosis, evaluating the disease progression as well as treatment in AD. This will open the door for early diagnosis of AD so as to prioritize management and optimize clinical outcomes..
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Affiliation(s)
- Sri Harsha Kanuri
- Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA
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Guo J, Cui B, Zheng J, Yu C, Zheng X, Yi L, Zhang S, Wang K. Platelet-derived microparticles and their cargos: The past, present and future. Asian J Pharm Sci 2024; 19:100907. [PMID: 38623487 PMCID: PMC11016590 DOI: 10.1016/j.ajps.2024.100907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 01/05/2024] [Accepted: 01/31/2024] [Indexed: 04/17/2024] Open
Abstract
All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.
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Affiliation(s)
- Jingwen Guo
- Department of Pharmacy, The First Hospital of China Medical University, Shenyang 110001 China
- School of Pharmacy, China Medical University, Shenyang 110122, China
| | - Bufeng Cui
- Department of Pharmacy, The First Hospital of China Medical University, Shenyang 110001 China
- School of Pharmacy, China Medical University, Shenyang 110122, China
| | - Jie Zheng
- Department of Pharmacy, The First Hospital of China Medical University, Shenyang 110001 China
- School of Pharmacy, China Medical University, Shenyang 110122, China
| | - Chang Yu
- School of Pharmacy, China Medical University, Shenyang 110122, China
| | - Xuran Zheng
- Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province, Health Sciences Institute of China Medical University, Shenyang 110122, China
| | - Lixin Yi
- School of Pharmacy, China Medical University, Shenyang 110122, China
- Department of Pharmacy, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China
| | - Simeng Zhang
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Keke Wang
- Department of Pharmacy, The First Hospital of China Medical University, Shenyang 110001 China
- School of Pharmacy, China Medical University, Shenyang 110122, China
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4
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Albert V, Subramanian A, Pati HP. Impact of Early Microparticle Release during Isolated Severe Traumatic Brain Injury: Correlation with Coagulopathy and Mortality. Neurol India 2024; 72:285-291. [PMID: 38691471 DOI: 10.4103/ni.ni_1159_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 06/16/2022] [Indexed: 05/03/2024]
Abstract
BACKGROUND Microparticles (MPs) have been implicated in thrombosis and endothelial dysfunction. Their involvement in early coagulopathy and in worsening of outcomes in isolated severe traumatic brain injury (sTBI) patients remains ill defined. OBJECTIVE We sought to quantify the circulatory MP subtypes derived from platelets (PMPs; CD42), endothelial cells (EMPs; CD62E), and those bearing tissue factor (TFMP; CD142) and analyze their correlation with early coagulopathy, thrombin generation, and in-hospital mortality. MATERIALS AND METHODS Prospective screening of sTBI patients was done. Blood samples were collected before blood and fluid transfusion. MP enumeration and characterization were performed using flow cytometry, and thrombin-antithrombin complex (TAT) levels were determined using enzyme-linked immunosorbent assay (ELISA). Circulating levels of procoagulant MPs were compared between isolated sTBI patients and age- and gender-matched healthy controls (HC). Patients were stratified according to their PMP, EMP, and TFMP levels, respectively (high ≥HC median and low < HC median). RESULTS Isolated sTBI resulted in an increased generation of PMPs (456.6 [228-919] vs. 249.1 [198.9-404.5]; P = 0.01) and EMPs (301.5 [118.8-586.7] vs. 140.9 [124.9-286]; P = 0.09) compared to HCs. Also, 5.3% of MPs expressed TF (380 [301-710]) in HCs, compared to 6.6% MPs (484 [159-484]; P = 0.87) in isolated sTBI patients. Early TBI-associated coagulopathy (TBI-AC) was seen in 50 (41.6%) patients. PMP (380 [139-779] vs. 523.9 [334-927]; P = 0.19) and EMP (242 [86-483] vs. 344 [168-605]; P = 0.81) counts were low in patients with TBI-AC, compared to patients without TBI-AC. CONCLUSION Our results suggest that enhanced cellular activation and procoagulant MP generation are predominant after isolated sTBI. TBI-AC was associated with low plasma PMPs count compared to the count in patients without TBI-AC. Low PMPs may be involved with the development of TBI-AC.
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Affiliation(s)
- Venencia Albert
- Departments of Laboratory Medicine, Jai Prakash Narayan Apex Trauma Centre, AIIMS, New Delhi, India
| | - Arulselvi Subramanian
- Departments of Laboratory Medicine, Jai Prakash Narayan Apex Trauma Centre, AIIMS, New Delhi, India
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Abdolalian M, Khalaf-Adeli E, Yari F, Hosseini S, Kiaeefar P. Presurgical circulating platelet-derived microparticles level as a risk factor of blood transfusion in patients with valve heart disease undergoing cardiac surgery. Transfus Clin Biol 2024; 31:19-25. [PMID: 38029957 DOI: 10.1016/j.tracli.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 11/17/2023] [Accepted: 11/21/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Cell-derived microparticles (MPs) are membrane vesicles that have emerged as a potential biomarker for various diseases and their clinical complications. This study investigates the role of MPs as a risk factor for blood transfusion in patients with valve heart disease undergoing cardiac surgery. METHODS Forty adult patients undergoing heart valve surgery with cardiopulmonary bypass (CPB) were enrolled, and venous blood samples were collected prior to surgical incision. Plasma rich in MPs was prepared by double centrifugation, and the concentration of MPs was determined using the Bradford method. Flow cytometry analysis was performed to determine MPs count and phenotype. Patients were divided into "with transfusion" (n = 18) and "without transfusion" (n = 22) groups based on red blood cell (RBC) transfusion. RESULTS There was no significant difference in MPs concentration between the "with transfusion" and "without transfusion" groups. Although the count of preoperative platelet-derived MPs (PMPs), monocyte-derived MPs (MMPs), and red cell-derived MPs (RMPs) was higher in "without transfusion" group, these differences were not statistically significant. The preoperative PMPs count was negatively correlated with RBC transfusion (P = 0.005, r = -0.65). Multivariate logistic regression analysis revealed that the count of CD41+ PMPs, Hemoglobin (Hb), and RBC count were risk factors for RBC transfusion. CONCLUSION This study suggests that the presurgical levels of PMPs, Hb, and RBC count can serve as risk factors of RBC transfusion in patients with valve heart disease undergoing cardiac surgery. The findings provide insights into the potential use of MPs as biomarkers for blood transfusion prediction in cardiac surgery.
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Affiliation(s)
- Mehrnaz Abdolalian
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Elham Khalaf-Adeli
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran; Department of Hematology, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Fatemeh Yari
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Saeid Hosseini
- Heart Valve Disease Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
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Zhang X, Yu S, Li X, Wen X, Liu S, Zu R, Ren H, Li T, Yang C, Luo H. Research progress on the interaction between oxidative stress and platelets: Another avenue for cancer? Pharmacol Res 2023; 191:106777. [PMID: 37080257 DOI: 10.1016/j.phrs.2023.106777] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 04/06/2023] [Accepted: 04/18/2023] [Indexed: 04/22/2023]
Abstract
Oxidative stress (OS) is a chemical imbalance between an oxidant and an antioxidant, causing damage to redox signaling and control or causing molecular damage. Unbalanced oxidative metabolism can produce excessive reactive oxygen species (ROS). These excess ROS can cause drastic changes in platelet metabolism and further affect platelet function. It will also lead to an increase in platelet procoagulant phenotype and cell apoptosis, which will increase the risk of thrombosis. The creation of ROS and subsequent platelet activation, adhesion, and recruitment are then further encouraged in an auto-amplifying loop by ROS produced from platelets. Meanwhile, cancer cells produce a higher concentration of ROS due to their fast metabolism and high proliferation rate. However, excessive ROS can result in damage to and modification of cellular macromolecules. The formation of cancer and its progression is strongly associated with oxidative stress and the resulting oxidative damage. In addition, platelets are an important part of the tumor microenvironment, and there is a significant cross-communication between platelets and cancer cells. Cancer cells alter the activation status of platelets, their RNA spectrum, proteome, and other properties. The "cloaking" of cancer cells by platelets providing physical protection，avoiding destruction from shear stress and the attack of immune cells, promoting tumor cell invasion.We explored the vicious circle interaction between ROS, platelets, and cancer in this review, and we believe that ROS can play a stimulative role in tumor growth and metastasis through platelets.
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Affiliation(s)
- Xingmei Zhang
- Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041 China; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610042, China
| | - Sisi Yu
- Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041 China
| | - Xiaobo Li
- Molecular Diagnostic Laboratory of Department of Microbiology and Immunology, 3201 Hospital Affiliated to Medical College of Xi'an Jiaotong University, Hanzhong 723099, China
| | - Xiaoxia Wen
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610042, China
| | - Shan Liu
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610042, China
| | - Ruiling Zu
- Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041 China
| | - Hanxiao Ren
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610042, China
| | - Tian Li
- School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China.
| | - Chaoguo Yang
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610042, China.
| | - Huaichao Luo
- Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041 China.
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7
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Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics. Exp Mol Med 2023; 55:1-12. [PMID: 36599934 PMCID: PMC9898542 DOI: 10.1038/s12276-022-00906-w] [Citation(s) in RCA: 85] [Impact Index Per Article: 42.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/25/2022] [Accepted: 10/31/2022] [Indexed: 01/05/2023] Open
Abstract
Senescence compromises the essential role that the endothelium plays in maintaining vascular homeostasis, so promoting endothelial dysfunction and the development of age-related vascular diseases. Their biological and clinical significance calls for strategies for identifying and therapeutically targeting senescent endothelial cells. While senescence and endothelial dysfunction have been studied extensively, distinguishing what is distinctly endothelial senescence remains a barrier to overcome for an effective approach to addressing it. Here, we review the mechanisms underlying endothelial senescence and the evidence for its clinical importance. Furthermore, we discuss the current state and the limitations in the approaches for the detection and therapeutic intervention of target cells, suggesting potential directions for future research.
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8
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Ge Y, Ye T, Fu S, Jiang X, Song H, Liu B, Wang G, Wang J. Research progress of extracellular vesicles as biomarkers in immunotherapy for non-small cell lung cancer. Front Immunol 2023; 14:1114041. [PMID: 37153619 PMCID: PMC10162406 DOI: 10.3389/fimmu.2023.1114041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 04/07/2023] [Indexed: 05/10/2023] Open
Abstract
Lung cancer is one of the most severe forms of malignancy and a leading cause of cancer-related death worldwide, of which non-small cell lung cancer (NSCLC) is the most primary type observed in the clinic. NSCLC is mainly treated with surgery, radiotherapy, and chemotherapy. Additionally, targeted therapy and immunotherapy have also shown promising results. Several immunotherapies, including immune checkpoint inhibitors, have been developed for clinical use and have benefited patients with NSCLC. However, immunotherapy faces several challenges like poor response and unknown effective population. It is essential to identify novel predictive markers to further advance precision immunotherapy for NSCLC. Extracellular vesicles (EVs) present an important research direction. In this review, we focus on the role of EVs as a biomarker in NSCLC immunotherapy considering various perspectives, including the definition and properties of EVs, their role as biomarkers in current NSCLC immunotherapy, and different EV components as biomarkers in NSCLC immunotherapy research. We describe the cross-talk between the role of EVs as biomarkers and novel technical approaches or research concepts in NSCLC immunotherapy, such as neoadjuvants, multi-omics analysis, and the tumour microenvironment. This review will provide a reference for future research to improve the benefits of immunotherapy for patients with NSCLC.
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Affiliation(s)
- Yang Ge
- Graduate School, Anhui University of Chinese Medicine, Hefei, China
| | - Ting Ye
- Graduate School, Anhui University of Chinese Medicine, Hefei, China
| | - Siyun Fu
- Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Xiaoying Jiang
- Department of Science and Technology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Hang Song
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Bin Liu
- Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
- *Correspondence: Bin Liu, ; Guoquan Wang, ; Jinghui Wang,
| | - Guoquan Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
- *Correspondence: Bin Liu, ; Guoquan Wang, ; Jinghui Wang,
| | - Jinghui Wang
- Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
- *Correspondence: Bin Liu, ; Guoquan Wang, ; Jinghui Wang,
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Castillo-Sanchez R, Churruca-Schuind A, Martinez-Ival M, Salazar EP. Cancer-associated Fibroblasts Communicate with Breast Tumor Cells Through Extracellular Vesicles in Tumor Development. Technol Cancer Res Treat 2022; 21:15330338221131647. [PMID: 36222020 PMCID: PMC9558853 DOI: 10.1177/15330338221131647] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Breast cancer is the leading cause of cancer death among women worldwide. In solid tumors, the microenvironment plays a critical role in tumor development, and it has been described a communication between the different cell types that conform the stroma, including fibroblasts, pericytes, adipocytes, immune cells and cancer-associated fibroblasts. Intercellular communication is bidirectional, complex, multifactorial and is mediated by the secretion of molecules and extracellular vesicles. The extracellular vesicles are vesicles limited by two membranes that are secreted by normal and cancer cells into the extracellular space. Extracellular vesicle cargo is complex and includes proteins, miRNAs, DNA and lipids, and their composition is specific to their parent cells. Extracellular vesicles are taken up for neighboring or distant cells. Particularly, extracellular vesicles from breast cancer cells are taken up for fibroblasts and it induces the activation of fibroblasts into cancer-associated fibroblasts. Interestingly, cancer associated fibroblasts release extracellular vesicles that are taken up for breast cancer cells and promote migration, invasion, proliferation, epithelial-mesenchymal transition, changes in metabolism, chemoresistance, evasion of immune system and remodeling of extracellular matrix. In addition, the enrichment of specific cargos in extracellular vesicles of breast cancer patients has been suggested to be used as biomarkers of the disease. Here we review the current literature about the intercommunication between tumor cells and cancer associated fibroblasts through extracellular vesicles in breast cancer.
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Affiliation(s)
| | | | | | - Eduardo Perez Salazar
- Eduardo Perez Salazar, PhD, Departamento de
Biologia Celular, Cinvestav-IPN, Av. IPN # 2508, Mexico City 07360, Mexico.
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The potential applications of microparticles in the diagnosis, treatment, and prognosis of lung cancer. Lab Invest 2022; 20:404. [PMID: 36064415 PMCID: PMC9444106 DOI: 10.1186/s12967-022-03599-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 08/18/2022] [Indexed: 12/02/2022]
Abstract
Microparticles (MPs) are 100–1000 nm heterogeneous submicron membranous vesicles derived from various cell types that express surface proteins and antigenic profiles suggestive of their cellular origin. MPs contain a diverse array of bioactive chemicals and surface receptors, including lipids, nucleic acids, and proteins, which are essential for cell-to-cell communication. The tumour microenvironment (TME) is enriched with MPs that can directly affect tumour progression through their interactions with receptors. Liquid biopsy, a minimally invasive test, is a promising alternative to tissue biopsy for the early screening of lung cancer (LC). The diverse biomolecular information from MPs provides a number of potential biomarkers for LC risk assessment, early detection, diagnosis, prognosis, and surveillance. Remodelling the TME, which profoundly influences immunotherapy and clinical outcomes, is an emerging strategy to improve immunotherapy. Tumour-derived MPs can reverse drug resistance and are ideal candidates for the creation of innovative and effective cancer vaccines. This review described the biogenesis and components of MPs and further summarised their main isolation and quantification methods. More importantly, the review presented the clinical application of MPs as predictive biomarkers in cancer diagnosis and prognosis, their role as therapeutic drug carriers, particularly in anti-tumour drug resistance, and their utility as cancer vaccines. Finally, we discussed current challenges that could impede the clinical use of MPs and determined that further studies on the functional roles of MPs in LC are required.
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Al-Koussa H, AlZaim I, El-Sabban ME. Pathophysiology of Coagulation and Emerging Roles for Extracellular Vesicles in Coagulation Cascades and Disorders. J Clin Med 2022; 11:jcm11164932. [PMID: 36013171 PMCID: PMC9410115 DOI: 10.3390/jcm11164932] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 05/20/2022] [Indexed: 11/16/2022] Open
Abstract
The notion of blood coagulation dates back to the ancient Greek civilization. However, the emergence of innovative scientific discoveries that started in the seventeenth century formulated the fundamentals of blood coagulation. Our understanding of key coagulation processes continues to evolve, as novel homeostatic and pathophysiological aspects of hemostasis are revealed. Hemostasis is a dynamic physiological process, which stops bleeding at the site of injury while maintaining normal blood flow within the body. Intrinsic and extrinsic coagulation pathways culminate in the homeostatic cessation of blood loss, through the sequential activation of the coagulation factors. Recently, the cell-based theory, which combines these two pathways, along with newly discovered mechanisms, emerged to holistically describe intricate in vivo coagulation mechanisms. The complexity of these mechanisms becomes evident in coagulation diseases such as hemophilia, Von Willebrand disease, thrombophilia, and vitamin K deficiency, in which excessive bleeding, thrombosis, or unnecessary clotting, drive the development and progression of diseases. Accumulating evidence implicates cell-derived and platelet-derived extracellular vesicles (EVs), which comprise microvesicles (MVs), exosomes, and apoptotic bodies, in the modulation of the coagulation cascade in hemostasis and thrombosis. As these EVs are associated with intercellular communication, molecular recycling, and metastatic niche creation, emerging evidence explores EVs as valuable diagnostic and therapeutic approaches in thrombotic and prothrombotic diseases.
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Affiliation(s)
- Houssam Al-Koussa
- Department of Pharmacology and Toxicology, Faculty of Medicine, The American University of Beirut, Beirut P.O. Box 11-0236, Lebanon
| | - Ibrahim AlZaim
- Department of Pharmacology and Toxicology, Faculty of Medicine, The American University of Beirut, Beirut P.O. Box 11-0236, Lebanon
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, The American University of Beirut, Beirut P.O. Box 11-0236, Lebanon
| | - Marwan E. El-Sabban
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, The American University of Beirut, Beirut P.O. Box 11-0236, Lebanon
- Correspondence: ; Tel.: +961-01-350-000 (ext. 4765)
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12
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EVs predict the outcomes in patients with acute myocardial infarction. Tissue Cell 2022; 77:101857. [DOI: 10.1016/j.tice.2022.101857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 06/15/2022] [Accepted: 06/16/2022] [Indexed: 11/23/2022]
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Li J, Duan H, Liu Y, Wang L, Zhou X. Biomaterial-Based Therapeutic Strategies for Obesity and Its Comorbidities. Pharmaceutics 2022; 14:1445. [PMID: 35890340 PMCID: PMC9320151 DOI: 10.3390/pharmaceutics14071445] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 07/02/2022] [Accepted: 07/04/2022] [Indexed: 02/01/2023] Open
Abstract
Obesity is a global public health issue that results in many health complications or comorbidities, including type 2 diabetes mellitus, cardiovascular disease, and fatty liver. Pharmacotherapy alone or combined with either lifestyle alteration or surgery represents the main modality to combat obesity and its complications. However, most anti-obesity drugs are limited by their bioavailability, target specificity, and potential toxic effects. Only a handful of drugs, including orlistat, liraglutide, and semaglutide, are currently approved for clinical obesity treatment. Thus, there is an urgent need for alternative treatment strategies. Based on the new revelation of the pathogenesis of obesity and the efforts toward the multi-disciplinary integration of materials, chemistry, biotechnology, and pharmacy, some emerging obesity treatment strategies are gradually entering the field of preclinical and clinical research. Herein, by analyzing the current situation and challenges of various new obesity treatment strategies such as small-molecule drugs, natural drugs, and biotechnology drugs, the advanced functions and prospects of biomaterials in obesity-targeted delivery, as well as their biological activities and applications in obesity treatment, are systematically summarized. Finally, based on the systematic analysis of biomaterial-based obesity therapeutic strategies, the future prospects and challenges in this field are proposed.
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Affiliation(s)
- Jing Li
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China; (J.L.); (H.D.); (Y.L.)
| | - Hongli Duan
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China; (J.L.); (H.D.); (Y.L.)
| | - Yan Liu
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China; (J.L.); (H.D.); (Y.L.)
| | - Lu Wang
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China; (J.L.); (H.D.); (Y.L.)
| | - Xing Zhou
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China; (J.L.); (H.D.); (Y.L.)
- Institute of Materia Medica and Center of Translational Medicine, College of Pharmacy, Army Medical University, Chongqing 400038, China
- Chongqing Key Laboratory of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, China
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14
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Boron M, Hauzer-Martin T, Keil J, Sun XL. Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures. TH OPEN 2022; 6:e194-e212. [PMID: 36046203 PMCID: PMC9273331 DOI: 10.1055/a-1801-2055] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 03/11/2022] [Indexed: 12/02/2022] Open
Abstract
Thrombomodulin (TM) is a type-I transmembrane protein that is mainly expressed on endothelial cells and plays important roles in many biological processes. Circulating TM of different forms are also present in biofluids, such as blood and urine. Soluble TM (sTM), comprised of several domains of TM, is the major circulating TM which is generated by either enzymatic or chemical cleavage of the intact protein under different conditions. Under normal conditions, sTM is present in low concentrations (<10 ng/mL) in the blood but is elevated in several pathological conditions associated with endothelial dysfunction such as cardiovascular, inflammatory, infection, and metabolic diseases. Therefore, sTM level has been examined for monitoring disease development, such as disseminated intravascular coagulation (DIC), sepsis and multiple organ dysfunction syndrome in patients with novel coronavirus disease 2019 (COVID-19) recently. In addition, microvesicles (MVs) that contain membrane TM (MV-TM) have been found to be released from activated cells which also contribute to levels of circulating TM in certain diseases. Several release mechanisms of sTM and MV-TM have been reported, including enzymatic, chemical, and TM mutation mechanisms. Measurements of sTM and MV-TM have been developed and explored as biomarkers in many diseases. In this review, we summarize all these advances in three categories as follows: (1) release mechanisms of circulating TM, (2) methods for measuring circulating TM in biological samples, and (3) correlation of circulating TM with diseases. Altogether, it provides a whole picture of recent advances on circulating TM in health and disease.
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Affiliation(s)
- Mallorie Boron
- Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United States
| | - Tiffany Hauzer-Martin
- Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United States
| | - Joseph Keil
- Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United States
| | - Xue-Long Sun
- Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United States
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15
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Bahmani L, Ullah M. Different Sourced Extracellular Vesicles and Their Potential Applications in Clinical Treatments. Cells 2022; 11:1989. [PMID: 35805074 PMCID: PMC9265969 DOI: 10.3390/cells11131989] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 06/19/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
Extracellular vesicles (EVs) include a heterogeneous group of natural cell-derived nanostructures that are increasingly regarded as promising biotherapeutic agents and drug delivery vehicles in human medicine. Desirable intrinsic properties of EVs including the ability to bypass natural membranous barriers and to deliver their unique biomolecular cargo to specific cell populations position them as fiercely competitive alternatives for currently available cell therapies and artificial drug delivery platforms. EVs with distinct characteristics can be released from various cell types into the extracellular environment as a means of transmitting bioactive components and altering the status of the target cell. Despite the existence of a large number of preclinical studies confirming the therapeutic efficacy of different originated EVs for treating several pathological conditions, in this review, we first provide a brief overview of EV biophysical properties with an emphasis on their intrinsic therapeutic benefits over cell-based therapies and synthetic delivery systems. Next, we describe in detail different EVs derived from distinct cell sources, compare their advantages and disadvantages, and recapitulate their therapeutic effects on various human disorders to highlight the progress made in harnessing EVs for clinical applications. Finally, knowledge gaps and concrete hurdles that currently hinder the clinical translation of EV therapies are debated with a futuristic perspective.
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Affiliation(s)
- Leila Bahmani
- Institute for Immunity and Transplantation, Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, CA 94304, USA;
- Molecular Medicine Department of Medicine, Stanford University, Palo Alto, CA 94304, USA
| | - Mujib Ullah
- Institute for Immunity and Transplantation, Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, CA 94304, USA;
- Molecular Medicine Department of Medicine, Stanford University, Palo Alto, CA 94304, USA
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16
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Stampouloglou PK, Siasos G, Bletsa E, Oikonomou E, Vogiatzi G, Kalogeras K, Katsianos E, Vavuranakis MA, Souvaliotis N, Vavuranakis M. The Role of Cell Derived Microparticles in Cardiovascular Diseases: Current Concepts. Curr Pharm Des 2022; 28:1745-1757. [DOI: 10.2174/1381612828666220429081555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 03/15/2022] [Indexed: 12/07/2022]
Abstract
Abstract:
Cardiovascular disease remains the main cause of human morbidity and mortality in the developed countries. Microparticles (MPs) are small vesicles originating from the cell membrane as a result of various stimuli and particularly of biological processes that constitute the pathophysiology of atherosclerosis, such as endothelial damage. They form vesicles that can transfer various molecules and signals to remote target cells without direct cell to cell interaction. Circulating microparticles have been associated with cardiovascular diseases. Therefore, many studies have been designed to further investigate the role of microparticles as biomarkers for diagnosis, prognosis, and disease monitoring. To this concept the pro-thrombotic and atherogenic potential of platelets and endothelial derived MPs has gain research interest especially concerning accelerate atherosclerosis and acute coronary syndrome triggering and prognosis. MPs especially of endothelial origin have been investigated in different clinical scenarios of heart failure and in association of left ventricular loading conditions. Finally, most cardiovascular risk factors present unique patterns of circulating MPs population, highlighting their pathophysiologic link to cardiovascular disease progression. In this review article we present a synopsis of the biogenesis and characteristics of microparticles, as well as the most recent data concerning their implication in the cardiovascular settings.
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Affiliation(s)
- Panagiota K. Stampouloglou
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
| | - Gerasimos Siasos
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Evanthia Bletsa
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
| | - Georgia Vogiatzi
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
| | - Konstantinos Kalogeras
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
| | - Efstratios Katsianos
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
| | - Michael-Andrew Vavuranakis
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
| | - Nektarios Souvaliotis
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
| | - Manolis Vavuranakis
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens. Greece
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17
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Luo L, Foster NC, Man KL, Brunet M, Hoey DA, Cox SC, Kimber SJ, El Haj AJ. Hydrostatic pressure promotes chondrogenic differentiation and microvesicle release from human embryonic and bone marrow stem cells. Biotechnol J 2022; 17:e2100401. [PMID: 34921593 DOI: 10.1002/biot.202100401] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 11/10/2022]
Abstract
Mechanical stimulation plays in an important role in regulating stem cell differentiation and their release of extracellular vesicles (EVs). In this study, effects of low magnitude hydrostatic pressure (HP) on the chondrogenic differentiation and microvesicle release from human embryonic stem cells (hESCs) and human bone marrow stem cells (hBMSCs) are examined. hESCs were differentiated into chondroprogenitors and then embedded in fibrin gels and subjected to HP (270 kPa, 1 Hz, 5 days per week). hBMSC pellets were differentiated in chondrogenic media and subjected to the same regime. HP significantly enhanced ACAN expression in hESCs. It also led to a significant increase in DNA content, sGAG content and total sGAG/DNA level in hBMSCs. Furthermore, HP significantly increased microvesicle protein content released from both cell types. These results highlight the benefit of HP bioreactor in promoting chondrogenesis and EV production for cartilage tissue engineering.
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Affiliation(s)
- Lu Luo
- Healthcare Technologies Institute, University of Birmingham, Birmingham, UK
- School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Nicola C Foster
- Healthcare Technologies Institute, University of Birmingham, Birmingham, UK
- Institute for Science and Technology in Medicine, Keele University, Stoke on Trent, UK
| | - Kenny L Man
- School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Mathieu Brunet
- School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - David A Hoey
- Department of Mechanical, Manufacturing, & Biomedical Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland
- Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
| | - Sophie C Cox
- School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Susan J Kimber
- School of Biological Sciences, University of Manchester, Manchester, UK
| | - Alicia J El Haj
- Healthcare Technologies Institute, University of Birmingham, Birmingham, UK
- Institute for Science and Technology in Medicine, Keele University, Stoke on Trent, UK
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18
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Marei I, Chidiac O, Thomas B, Pasquier J, Dargham S, Robay A, Vakayil M, Jameesh M, Triggle C, Rafii A, Jayyousi A, Al Suwaidi J, Abi Khalil C. Angiogenic content of microparticles in patients with diabetes and coronary artery disease predicts networks of endothelial dysfunction. Cardiovasc Diabetol 2022; 21:17. [PMID: 35109843 PMCID: PMC8812242 DOI: 10.1186/s12933-022-01449-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 01/20/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Elevated endothelial microparticles (EMPs) levels are surrogate markers of vascular dysfunction. We analyzed EMPs with apoptotic characteristics and assessed the angiogenic contents of microparticles in the blood of patients with type 2 diabetes (T2D) according to the presence of coronary artery disease (CAD). METHODS A total of 80 participants were recruited and equally classified as (1) healthy without T2D, (2) T2D without cardiovascular complications, (3) T2D and chronic coronary artery disease (CAD), and (4) T2D and acute coronary syndrome (ACS). MPs were isolated from the peripheral circulation, and EMPs were characterized using flow cytometry of CD42 and CD31. CD62E was used to determine EMPs' apoptotic/activation state. MPs content was extracted and profiled using an angiogenesis array. RESULTS Levels of CD42- CD31 + EMPs were significantly increased in T2D with ACS (257.5 ± 35.58) when compared to healthy subjects (105.7 ± 12.96, p < 0.01). There was no significant difference when comparing T2D with and without chronic CAD. The ratio of CD42-CD62 +/CD42-CD31 + EMPs was reduced in all T2D patients, with further reduction in ACS when compared to chronic CAD, reflecting a release by apoptotic endothelial cells. The angiogenic content of the full population of MPs was analyzed. It revealed a significant differential expression of 5 factors in patients with ACS and diabetes, including TGF-β1, PD-ECGF, platelet factor 4, serpin E1, and thrombospondin 1. Ingenuity Pathway Analysis revealed that those five differentially expressed molecules, mainly TGF-β1, inhibit key pathways involved in normal endothelial function. Further comparison of the three diabetes groups to healthy controls and diabetes without cardiovascular disease to diabetes with CAD identified networks that inhibit normal endothelial cell function. Interestingly, DDP-IV was the only differentially expressed protein between chronic CAD and ACS in patients with diabetes. CONCLUSION Our data showed that the release of apoptosis-induced EMPs is increased in diabetes, irrespective of CAD, ACS patients having the highest levels. The protein contents of MPs interact in networks that indicate vascular dysfunction.
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Affiliation(s)
- Isra Marei
- Department of Pharmacology, Weill Cornell Medicine-Qatar, Doha, Qatar
- National Heart and Lung Institute, Imperial College London, London, UK
- Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Omar Chidiac
- Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Binitha Thomas
- Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Jennifer Pasquier
- Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Soha Dargham
- Biostatistics Core, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Amal Robay
- Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Muneera Vakayil
- Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | | | | | - Arash Rafii
- Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Amin Jayyousi
- Department of Endocrinology, Hamad Medical Corporation, Doha, Qatar
| | | | - Charbel Abi Khalil
- Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar.
- Heart Hospital, Hamad Medical Corporation, Doha, Qatar.
- Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA.
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19
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The procoagulant effects of extracellular vesicles derived from hypoxic endothelial cells can be selectively inhibited by inorganic nitrite. Nitric Oxide 2022; 122-123:6-18. [DOI: 10.1016/j.niox.2022.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 02/11/2022] [Accepted: 02/14/2022] [Indexed: 11/20/2022]
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20
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Therapeutic applications of mitochondrial transplantation. Biochimie 2022; 195:1-15. [DOI: 10.1016/j.biochi.2022.01.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 01/06/2022] [Accepted: 01/07/2022] [Indexed: 12/12/2022]
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21
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Maphumulo SC, Pretorius E. Role of Circulating Microparticles in Type 2 Diabetes Mellitus: Implications for Pathological Clotting. Semin Thromb Hemost 2021; 48:188-205. [PMID: 34959250 DOI: 10.1055/s-0041-1740150] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a multifactorial chronic metabolic disease characterized by chronic hyperglycemia due to insulin resistance and a deficiency in insulin secretion. The global diabetes pandemic relates primarily to T2DM, which is the most prevalent form of diabetes, accounting for over 90% of all cases. Chronic low-grade inflammation, triggered by numerous risk factors, and the chronic activation of the immune system are prominent features of T2DM. Here we highlight the role of blood cells (platelets, and red and white blood cells) and vascular endothelial cells as drivers of systemic inflammation in T2DM. In addition, we discuss the role of microparticles (MPs) in systemic inflammation and hypercoagulation. Although once seen as inert by-products of cell activation or destruction, MPs are now considered to be a disseminated storage pool of bioactive effectors of thrombosis, inflammation, and vascular function. They have been identified to circulate at elevated levels in the bloodstream of individuals with increased risk of atherothrombosis or cardiovascular disease, two significant hallmark conditions of T2DM. There is also general evidence that MPs activate blood cells, express proinflammatory and coagulant effects, interact directly with cell receptors, and transfer biological material. MPs are considered major players in the pathogenesis of many systemic inflammatory diseases and may be potentially useful biomarkers of disease activity and may not only be of prognostic value but may act as novel therapeutic targets.
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Affiliation(s)
| | - Etheresia Pretorius
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
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22
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Stępień EŁ, Rząca C, Moskal P. Novel biomarker and drug delivery systems for theranostics – extracellular vesicles. BIO-ALGORITHMS AND MED-SYSTEMS 2021. [DOI: 10.1515/bams-2021-0183] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Abstract
Extracellular vesicles (EVs) are nano- and micro-sized double-layered membrane entities derived from most cell types and released into biological fluids. Biological properties (cell-uptake, biocompatibility), and chemical (composition, structure) or physical (size, density) characteristics make EVs a good candidate for drug delivery systems (DDS). Recent advances in the field of EVs (e.g., scaling-up production, purification) and developments of new imaging methods (total-body positron emission tomography [PET]) revealed benefits of radiolabeled EVs in diagnostic and interventional medicine as a potential DDs in theranostics.
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Affiliation(s)
- Ewa Ł. Stępień
- M. Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University , Krakow , Poland
- Total-Body Jagiellonian-PET Laboratory, Jagiellonian University , Kraków , Poland
- Theranostics Center, Jagiellonian University , Kraków , Poland
| | - Carina Rząca
- M. Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University , Krakow , Poland
- Theranostics Center, Jagiellonian University , Kraków , Poland
| | - Paweł Moskal
- M. Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University , Krakow , Poland
- Total-Body Jagiellonian-PET Laboratory, Jagiellonian University , Kraków , Poland
- Theranostics Center, Jagiellonian University , Kraków , Poland
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23
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Wurtzel JGT, Lazar S, Sikder S, Cai KQ, Astsaturov I, Weyrich AS, Rowley JW, Goldfinger LE. Platelet microRNAs inhibit primary tumor growth via broad modulation of tumor cell mRNA expression in ectopic pancreatic cancer in mice. PLoS One 2021; 16:e0261633. [PMID: 34936674 PMCID: PMC8694476 DOI: 10.1371/journal.pone.0261633] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 12/06/2021] [Indexed: 11/19/2022] Open
Abstract
We investigated the contributions of platelet microRNAs (miRNAs) to the rate of growth and regulation of gene expression in primary ectopic tumors using mouse models. We previously identified an inhibitory role for platelets in solid tumor growth, mediated by tumor infiltration of platelet microvesicles (microparticles) which are enriched in platelet-derived miRNAs. To investigate the specific roles of platelet miRNAs in tumor growth models, we implanted pancreatic ductal adenocarcinoma cells as a bolus into mice with megakaryocyte-/platelet-specific depletion of mature miRNAs. We observed an ~50% increase in the rate of growth of ectopic primary tumors in these mice compared to controls including at early stages, associated with reduced apoptosis in the tumors, in particular in tumor cells associated with platelet microvesicles-which were depleted of platelet-enriched miRNAs-demonstrating a specific role for platelet miRNAs in modulation of primary tumor growth. Differential expression RNA sequencing of tumor cells isolated from advanced primary tumors revealed a broad cohort of mRNAs modulated in the tumor cells as a function of host platelet miRNAs. Altered genes comprised 548 up-regulated transcripts and 43 down-regulated transcripts, mostly mRNAs altogether spanning a variety of growth signaling pathways-notably pathways related to epithelial-mesenchymal transition-in tumor cells from platelet miRNA-deleted mice compared with those from control mice. Tumors in platelet miRNA-depleted mice showed more sarcomatoid growth and more advanced tumor grade, indicating roles for host platelet miRNAs in tumor plasticity. We further validated increased protein expression of selected genes associated with increased cognate mRNAs in the tumors due to platelet miRNA depletion in the host animals, providing proof of principle of widespread effects of platelet miRNAs on tumor cell functional gene expression in primary tumors in vivo. Together, these data demonstrate that platelet-derived miRNAs modulate solid tumor growth in vivo by broad-spectrum restructuring of the tumor cell transcriptome.
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Affiliation(s)
- Jeremy G. T. Wurtzel
- Division of Hematology, Department of Medicine, Cardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States of America
| | - Sophia Lazar
- Division of Hematology, Department of Medicine, Cardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States of America
| | - Sonali Sikder
- Molecular Therapeutics Program and The Marvin & Concetta Greenberg Pancreatic Cancer Institute, Fox Chase Cancer Center, Philadelphia, PA, United States of America
| | - Kathy Q. Cai
- Cancer Biology Program and Histopathology Facility, Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA, United States of America
| | - Igor Astsaturov
- Molecular Therapeutics Program and The Marvin & Concetta Greenberg Pancreatic Cancer Institute, Fox Chase Cancer Center, Philadelphia, PA, United States of America
| | - Andrew S. Weyrich
- Molecular Medicine Program, Pathology Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States of America
| | - Jesse W. Rowley
- Molecular Medicine Program, Pulmonary Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States of America
| | - Lawrence E. Goldfinger
- Division of Hematology, Department of Medicine, Cardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States of America
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24
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Tu AB, Lewis JS. Biomaterial-based immunotherapeutic strategies for rheumatoid arthritis. Drug Deliv Transl Res 2021; 11:2371-2393. [PMID: 34414564 PMCID: PMC8376117 DOI: 10.1007/s13346-021-01038-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/19/2021] [Indexed: 02/08/2023]
Abstract
Rheumatoid arthritis (RA) is an extremely painful autoimmune disease characterized by chronic joint inflammation leading to the erosion of adjacent cartilage and bone. Rheumatoid arthritis pathology is primarily driven by inappropriate infiltration and activation of immune cells within the synovium of the joint. There is no cure for RA. As such, manifestation of symptoms entails lifelong management via various therapies that aim to generally dampen the immune system or impede the function of immune mediators. However, these treatment strategies lead to adverse effects such as toxicity, general immunosuppression, and increased risk of infection. In pursuit of safer and more efficacious therapies, many emerging biomaterial-based strategies are being developed to improve payload delivery, specific targeting, and dose efficacy, and to mitigate adverse reactions and toxicity. In this review, we highlight biomaterial-based approaches that are currently under investigation to circumvent the limitations of conventional RA treatments.
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Affiliation(s)
- Allen B Tu
- Department of Biomedical Engineering, University of California, 1 Shields Ave, Davis , CA, 95616, USA
| | - Jamal S Lewis
- Department of Biomedical Engineering, University of California, 1 Shields Ave, Davis , CA, 95616, USA.
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25
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Kotlyarov S. Diversity of Lipid Function in Atherogenesis: A Focus on Endothelial Mechanobiology. Int J Mol Sci 2021; 22:11545. [PMID: 34768974 PMCID: PMC8584259 DOI: 10.3390/ijms222111545] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/12/2021] [Accepted: 10/21/2021] [Indexed: 12/12/2022] Open
Abstract
Atherosclerosis is one of the most important problems in modern medicine. Its high prevalence and social significance determine the need for a better understanding of the mechanisms of the disease's development and progression. Lipid metabolism and its disorders are one of the key links in the pathogenesis of atherosclerosis. Lipids are involved in many processes, including those related to the mechanoreception of endothelial cells. The multifaceted role of lipids in endothelial mechanobiology and mechanisms of atherogenesis are discussed in this review. Endothelium is involved in ensuring adequate vascular hemodynamics, and changes in blood flow characteristics are detected by endothelial cells and affect their structure and function.
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Affiliation(s)
- Stanislav Kotlyarov
- Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia
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Macedo-da-Silva J, Santiago VF, Rosa-Fernandes L, Marinho CRF, Palmisano G. Protein glycosylation in extracellular vesicles: Structural characterization and biological functions. Mol Immunol 2021; 135:226-246. [PMID: 33933815 DOI: 10.1016/j.molimm.2021.04.017] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/13/2021] [Accepted: 04/20/2021] [Indexed: 02/07/2023]
Abstract
Extracellular vesicles (EVs) are lipid bilayer-enclosed particles involved in intercellular communication, delivery of biomolecules from donor to recipient cells, cellular disposal and homeostasis, potential biomarkers and drug carriers. The content of EVs includes DNA, lipids, metabolites, proteins, and microRNA, which have been studied in various diseases, such as cancer, diabetes, pregnancy, neurodegenerative, and cardiovascular disorders. EVs are enriched in glycoconjugates and exhibit specific glycosignatures. Protein glycosylation is a co- and post-translational modification (PTM) that plays an important role in the expression and function of exosomal proteins. N- and O-linked protein glycosylation has been mapped in exosomal proteins. The purpose of this review is to highlight the importance of glycosylation in EVs proteins. Initially, we describe the main PTMs in EVs with a focus on glycosylation. Then, we explore glycan-binding proteins describing the main findings of studies that investigated the glycosylation of EVs in cancer, pregnancy, infectious diseases, diabetes, mental disorders, and animal fluids. We have highlighted studies that have developed innovative methods for studying the content of EVs. In addition, we present works related to lipid glycosylation. We explored the content of studies deposited in public databases, such as Exocarta and Vesiclepedia. Finally, we discuss analytical methods for structural characterization of glycoconjugates and present an overview of the critical points of the study of glycosylation EVs, as well as perspectives in this field.
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Affiliation(s)
- Janaina Macedo-da-Silva
- Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
| | - Verônica F Santiago
- Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
| | - Livia Rosa-Fernandes
- Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
| | - Claudio R F Marinho
- Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
| | - Giuseppe Palmisano
- Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
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Husa P, Snopkova S, Zavrelova J, Zlamal F, Svacinka R, Husa P. Circulating microparticles in patients with chronic hepatitis C and changes during direct-acting antiviral therapy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021; 165:146-151. [PMID: 33928944 DOI: 10.5507/bp.2021.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 04/14/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Microparticles (MPs) are heterogeneous vesicles derived from membranes of different cells. Between 70 to 90% of MPs detected in blood originate from platelets. The release of MPs is associated with proinflammatory and procoagulant states. Elevated levels of MPs have been found in different diseases. We investigated MPs levels in patients with chronic hepatitis C (CHC) and changes in level during treatment using direct-acting antivirotics (DAA). PATIENTS AND METHODS Thirty-six patients with CHC and forty healthy volunteers were included in the study. Concentrations of MPs were determined indirectly by measuring their procoagulant activity in plasma at baseline, end of therapy (EOT), and 12 weeks after EOT when the sustained virological response was assessed (SVR12). RESULTS All patients achieved SVR12, which was associated with rapid improvement of markers of liver damage and function as well as liver stiffness (P=0.002). MPs levels were significantly higher in CHC patients than in healthy volunteers (P<0.001). No statistically significant decrease was found observed between baseline and SVR12 (P=0,330). Analysis of subpopulations with minimal fibrosis F0-1 (P=0.647), advanced fibrosis F2-4 (P=0.370), women(P=0.847), men (P=0.164) and genotype 1 (P=0.077) showed no significant changes during the follow-up period. CONCLUSIONS MPs levels are higher in CHC patients and remain elevated shortly after achieving SVR. Higher concentrations of MPs in plasma are probably caused by a chronic uncontrolled exaggerated inflammatory response caused by CHC. Longer observation would probably confirm the significance of MPs levels decrease because normalization of liver function, inflammation, and structure after SVR requires more than 12 weeks.
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Affiliation(s)
- Petr Husa
- Department of Infectious Diseases, University Hospital Brno, Jihlavska 20, 62500 Brno, Czech Republic.,Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
| | - Svatava Snopkova
- Department of Infectious Diseases, University Hospital Brno, Jihlavska 20, 62500 Brno, Czech Republic.,Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
| | - Jirina Zavrelova
- Department of Hematology, University Hospital Brno, Jihlavska 20, 62500 Brno, Czech Republic
| | - Filip Zlamal
- Research Centre for Toxic Compounds in the Environment, Masaryk University, Kamenice 5, 60200 Brno, Czech Republic
| | - Radek Svacinka
- Department of Infectious Diseases, University Hospital Brno, Jihlavska 20, 62500 Brno, Czech Republic.,Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
| | - Petr Husa
- Department of Infectious Diseases, University Hospital Brno, Jihlavska 20, 62500 Brno, Czech Republic.,Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
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Nader E, Conran N, Romana M, Connes P. Vasculopathy in Sickle Cell Disease: From Red Blood Cell Sickling to Vascular Dysfunction. Compr Physiol 2021; 11:1785-1803. [PMID: 33792905 DOI: 10.1002/cphy.c200024] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Sickle cell disease (SCD) is a hereditary disorder that leads to the production of an abnormal hemoglobin, hemoglobin S (HbS). HbS polymerizes in deoxygenated conditions, which can prompt red blood cell (RBC) sickling and leaves the RBCs more rigid, fragile, and prone to hemolysis. SCD patients suffer from a plethora of complications, ranging from acute complications, such as characteristic, frequent, and debilitating vaso-occlusive episodes to chronic organ damage. While RBC sickling is the primary event at the origin of vaso-occlusive processes, other factors that can further increase RBC transit times in the microcirculation may also be required to precipitate vaso-occlusive processes. The adhesion of RBC and leukocytes to activated endothelium and the formation of heterocellular aggregates, as well as increased blood viscosity, are among the mechanisms involved in slowing the progress of RBCs in deoxygenated vascular areas, favoring RBC sickling and promoting vascular occlusion. Chronic inflammatory processes and oxidative stress, which are perpetuated by hemolytic events and ischemia-reperfusion injury, result in this pan cellular activation and some acute events, such as stroke and acute chest syndrome, as well as chronic end-organ damage. Furthermore, impaired vasodilation and vasomotor hyperresponsiveness in SCD also contribute to vaso-occlusive processes. Treating SCD as a vascular disease in addition to its hematological perspective, the present article looks at the interplay between abnormal RBC physiology/integrity, vascular dysfunction and clinical severity in SCD, and discusses existing therapies and novel drugs in development that may ameliorate vascular complications in the disease. © 2021 American Physiological Society. Compr Physiol 11:1785-1803, 2021.
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Affiliation(s)
- Elie Nader
- Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team Vascular Biology and Red Blood Cell, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.,Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France
| | - Nicola Conran
- Hematology Center, University of Campinas - UNICAMP, Cidade Universitária, Campinas-SP, Brazil
| | - Marc Romana
- Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France.,Université des Antilles, UMR_S1134, BIGR, Pointe-à-Pitre, France.,Université de Paris, UMR_S1134, BIGR, INSERM, Paris, France
| | - Philippe Connes
- Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team Vascular Biology and Red Blood Cell, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.,Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France
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Chatterjee V, Yang X, Ma Y, Cha B, Meegan JE, Wu M, Yuan SY. Endothelial microvesicles carrying Src-rich cargo impair adherens junction integrity and cytoskeleton homeostasis. Cardiovasc Res 2021; 116:1525-1538. [PMID: 31504252 PMCID: PMC7314637 DOI: 10.1093/cvr/cvz238] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 08/06/2019] [Accepted: 08/29/2019] [Indexed: 12/12/2022] Open
Abstract
Aims Microvesicles (MVs) conduct intercellular communication and impact diverse biological processes by transferring bioactive cargos to other cells. We investigated whether and how endothelial production of MVs contribute to vascular dysfunction during inflammation. Methods and results We measured the levels and molecular properties of endothelial-derived MVs (EC-MVs) from mouse plasma following a septic injury elicited by cecal ligation and puncture, as well as those from supernatants of cultured endothelial cells stimulated by inflammatory agents including cytokines, thrombin, and complement 5a. The mouse studies showed that sepsis caused a significant increase in total plasma vesicles and VE-cadherin+ EC-MVs compared to sham control. In cultured ECs, different inflammatory agents caused diverse patterns of EC-MV production and cargo contents. When topically applied to endothelial cells, EC-MVs induced a cytoskeleton-junction response characterized by myosin light chain phosphorylation, contractile fibre reorganization, VE-cadherin phosphorylation, and adherens junction dissociation, functionally measured as increased albumin transendothelial flux and decreased barrier resistance. The endothelial response was coupled with protein tyrosine phosphorylation promoted by MV cargo containing c-Src kinase, whereas MVs produced from c-Src deficient cells did not exert barrier-disrupting effects. Additionally, EC-MVs contribute to endothelial inflammatory injury by promoting neutrophil-endothelium adhesion and release of neutrophil extracellular traps containing citrullinated histones and myeloperoxidase, a response unaltered by c-Src knockdown. Conclusion Endothelial-derived microparticles cause endothelial barrier dysfunction by impairing adherens junctions and activating neutrophils. The signalling mechanisms underlying the endothelial cytoskeleton-junction response to EC-MVs involve protein phosphorylation promoted by MV cargo carrying c-Src. However, EC-MV-induced neutrophil activation was not dependent on c-Src.
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Affiliation(s)
- Victor Chatterjee
- Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
| | - Xiaoyuan Yang
- Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
| | - Yonggang Ma
- Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
| | - Byeong Cha
- Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
| | - Jamie E Meegan
- Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
| | - Mack Wu
- Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
| | - Sarah Y Yuan
- Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.,Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
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30
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Li D, Jia H, Zhang H, Lv M, Liu J, Zhang Y, Huang T, Huang B. TLR4 signaling induces the release of microparticles by tumor cells that regulate inflammatory cytokine IL-6 of macrophages via microRNA let-7b. Oncoimmunology 2021; 1:687-693. [PMID: 22934260 PMCID: PMC3429572 DOI: 10.4161/onci.19854] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Tumor cells expressing TLRs is generally recognized to mediate tumor inflammation. However, whether and how tumor TLR signaling pathways negatively regulate tumor inflammation remains unclear. In this report, we find that TLR4 signaling of H22 hepatocarcinoma tumor cells is transduced through MyD88 pathway to actin cytoskeletons, leading to the release of microparticles (MPs), the cellular membrane-derived vesicles. As a result, tumor macrophages take up MPs and acquire MP-contained microRNA let-7b, which attenuates tumor inflammation by targeting proinflammatory cytokine IL-6. Thus, tumor TLR signaling, contrary to the original promoting effect, may play an opposite role in downregulating tumor inflammation through MP pathways.
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Affiliation(s)
- Dapeng Li
- Department of Biochemistry and Molecular Biology; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, China ; Department of Breast and Thyroid Surgery; Union Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, China
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Ghaffari F, Rasmi Y, Seyed Mohammadzad MH, Seyedi S, Shirpoor A, Roshani-Asl E, Saboory E. Increased circulating platelet and endothelial-derived microparticles in patients with cardiac syndrome X. ARYA ATHEROSCLEROSIS 2021; 17:1-10. [PMID: 34703482 PMCID: PMC8519618 DOI: 10.22122/arya.v17i0.2094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 06/02/2020] [Indexed: 11/09/2022]
Abstract
BACKGROUND Cardiac syndrome X (CSX) has been associated with endothelial dysfunction and inflammation. We conducted a case-control study to evaluate the association between plateletý and endothelial-derived microparticles (PMPs and EMPs), as specific quantitative plasma markers of endothelial dysfunction, and the presence of CSX. METHODS The present study was conducted on 40 CSX patients and 19 healthy individuals. C-reactive protein (CRP), and hematological and biochemical parameters were evaluated. The MP concentration in platelet-poor plasma (PPP) was quantitatively determined through flow cytometry using specific anti-human CD31, CD41a, CD62E, and CD144 antibodies. RESULTS The mean platelet volume (MPV) and positive CRP rate (≥ 3.8 mg/l) were higher in patients compared to controls (P = 0.020 and P = 0.010, respectively). The CD62E+, CD144+, and CD31+41- EMPs, as well as CD41+ and CD31+CD41+ PMPs showed significant increase in CSX patients compared to controls (P < 0.050). There were direct correlations between the mean percentage of detected EMPs and PMPs as well as between their expression intensity; however, a reverse correlation was seen between the percentage of MPs and CD144 and CD41. Moreover, the MP level was reversely associated with prothrombin time (PT) and partial thromboplastin time (PTT) values. Only CD31+CD41+ PMP was correlated with CRP. CONCLUSION It seems that EMPs and PMPs increase in CSX, which may contribute to various processes involved in the development of this syndrome.
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Affiliation(s)
- Fereshteh Ghaffari
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Yousef Rasmi
- Professor, Cellular and Molecular Research Center AND Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mir Hossein Seyed Mohammadzad
- Associate Professor, Department of Cardiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Shahram Seyedi
- Assistant Professor, Department of Immunology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Alireza Shirpoor
- Professor, Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Elmira Roshani-Asl
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ehsan Saboory
- Professor, Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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Navas-Acien A, Martinez-Morata I, Hilpert M, Rule A, Shimbo D, LoIacono NJ. Early Cardiovascular Risk in E-cigarette Users: the Potential Role of Metals. Curr Environ Health Rep 2020; 7:353-361. [PMID: 33242201 PMCID: PMC7959158 DOI: 10.1007/s40572-020-00297-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2020] [Indexed: 01/18/2023]
Abstract
PURPOSE OF REVIEW Electronic cigarettes (e-cigs) are a source of metals. Epidemiologic and experimental evidence support that metals are toxic to the cardiovascular system. Little is known, however, about the role that e-cig metals may play as toxicants for the possible cardiovascular effects of e-cig use. The goal of this narrative review is to summarize the evidence on e-cig use and metal exposure and on e-cig use and cardiovascular toxicity and discuss the research needs. RECENT FINDINGS In vitro studies show cytotoxicity and increased oxidative stress in myocardial cells and vascular endothelial cells exposed to e-liquids and e-cig aerosols, with effects partially reversed with antioxidant treatment. There is some evidence that the heating coil plays a role in cell toxicity. Mice exposed to e-cigs for several weeks showed higher levels of oxidative stress, inflammation, platelet activation, and thrombogenesis. Cross-over clinical experiments show e-cig use alters nitric oxide-mediated flow-mediated dilation, endothelial progenitor cells, and arterial stiffness. Cross-sectional evidence from large nationally representative samples in the USA support that e-cig use is associated with self-reported myocardial infarction. Smaller studies found associations of e-cig use with higher oxidized low-density protein and heart variability compared to healthy controls. Numerous studies have measured elevated levels of toxic metals in e-cig aerosols including lead, nickel, chromium, and manganese. Arsenic has been measured in some e-liquids. Several of these metals are well known to be cardiotoxic. Numerous studies show that e-cigs are a source of cardiotoxic metals. Experimental studies (in vitro, in vivo, and clinical studies) show acute toxicity of e-cigs to the vascular system. Studies of long-term toxicity in animals and humans are missing. Longitudinal studies with repeated measures of metal exposure and subclinical cardiovascular outcomes (e.g., coronary artery calcification) could contribute to determine the long-term cardiovascular effects of e-cigs and the potential role of metals in those effects.
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Affiliation(s)
- Ana Navas-Acien
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th Street, New York, NY, 10032, USA
| | - Irene Martinez-Morata
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th Street, New York, NY, 10032, USA
| | - Markus Hilpert
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th Street, New York, NY, 10032, USA
| | - Ana Rule
- Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA
| | - Daichi Shimbo
- Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Nancy J LoIacono
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th Street, New York, NY, 10032, USA.
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Liu CS, Li CI, Guo YC, Lin CH, Lin WY, Liu CH, Wang MC, Yang CW, Yang SY, Li TC, Lin CC. Independent associations of urinary albumin-to-creatinine ratio and serum cystatin C with carotid intima-media thickness in community-living Taiwanese adults. BMC Nephrol 2020; 21:454. [PMID: 33129312 PMCID: PMC7603773 DOI: 10.1186/s12882-020-02123-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 10/26/2020] [Indexed: 11/29/2022] Open
Abstract
Background Renal function is a key factor of cardiovascular disease. Carotid intima-media thickness (IMT) has been widely used as a marker of early subclinical atherosclerosis. The determinants of cystatin C, a novel marker of renal function, have not been extensively studied in the Asian population. This study aimed to assess the determinants of cystatin C and explore whether carotid thickening was associated with urinary albumin-creatinine ratio and cystatin C in community-living Taiwanese adults. Methods A cross-sectional study was conducted on participants from Taichung City, Taiwan. All the participants underwent carotid ultrasonography. Carotid IMT-mean and IMT-maximum were derived. Kidney biomarkers were measured on the basis of urinary albumin-to-creatinine ratio (ACR) and cystatin C. Multiple linear regression analysis was used. Results A total of 1032 individuals were recruited, and 469 (45.44%) of them were men. An increased cystatin C level was significantly associated with older age, male gender, lack of physical activity, low HDL cholesterol, abdominal obesity, high hs-CRP, and high ACR. The multivariate-adjusted mean carotid IMT-mean and IMT-maximum values significantly increased by 80.49 and 195.23 μm for every one unit of increase in cystatin C level and by 0.07 and 0.14 μm for every one unit of increase in ACR, respectively (all p < 0.001 except ACR on IMT-maximum with p < 0.01). Lack of physical activity, low HDL, abdominal obesity, high hs-CRP, and high ACR were the determinants of cystatin C. Conclusion Cystatin C and ACR were strongly and linearly associated with carotid thickening, a marker of subclinical atherosclerosis. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-020-02123-x.
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Affiliation(s)
- Chiu-Shong Liu
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Ing Li
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Yuh-Cherng Guo
- Department of Neurology, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsueh Lin
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Yuan Lin
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chung-Hsiang Liu
- Department of Neurology, China Medical University Hospital, Taichung, Taiwan
| | - Mu-Cyun Wang
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chuan-Wei Yang
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Shing-Yu Yang
- Department of Public Health, College of Public Health, China Medical University, 91 Hsueh-Shih Road, Taichung, 40421, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, 91 Hsueh-Shih Road, Taichung, 40421, Taiwan. .,Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan.
| | - Cheng-Chieh Lin
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan.,Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
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Bar-Sela G, Cohen I, Avisar A, Loven D, Aharon A. Circulating blood extracellular vesicles as a tool to assess endothelial injury and chemotherapy toxicity in adjuvant cancer patients. PLoS One 2020; 15:e0240994. [PMID: 33108394 PMCID: PMC7591065 DOI: 10.1371/journal.pone.0240994] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 10/06/2020] [Indexed: 01/08/2023] Open
Abstract
Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles, which represent a potential source for cancer biomarker discovery. We assess EVs characteristics as a tool to evaluate the endothelial and anti-tumor treatment injury during adjuvant chemotherapy in breast (BC) and colon cancer (CC) patients. Blood samples were taken from 29 BC and 25 CC patients before and after chemotherapy, as well as from healthy control donors (HC). Circulating blood EVs were isolated and characterized by size/concentration, membrane antigens for cell origin, thrombogenicity, and protein content. We observed higher EVs concentration and particle size in CC patients after chemotherapy compared with HC. Higher levels of endothelial EVs (CD144-positive) and vascular endothelial growth factor receptor 1 (VEGFR1), apparently as an indication of endothelial dysfunction, were found in all cancer patients, regardless of a given treatment, compared to HC. Levels of EVs labeled CD62E, CD34+41-, the lymphocyte markers CD11+ and CD-14+, Annexin-V, and the coagulation proteins TF and TFPI, however, sometimes demonstrate significant differences between patients, although HC did not show significant differences between patients pre- and post-chemotherapy. Most importantly, increasing levels of EVs encapsulated Angiostatin were found in patients with CC, while chemotherapy treatment leads to its notable rise in circulating blood EVs. Our results demonstrate the potential of EVs encapsulated Angiostatin as a tool to evaluate endothelial damage during adjuvant chemotherapy in BC and CC patients.
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Affiliation(s)
- Gil Bar-Sela
- Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Cancer Center, Emek Medical Center, Afula, Israel
| | - Idan Cohen
- Cancer Center, Emek Medical Center, Afula, Israel
| | | | - David Loven
- Cancer Center, Emek Medical Center, Afula, Israel
| | - Anat Aharon
- Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Hematology and Bone Marrow Transplantation, Sourasky Medical Center, Tel Aviv, Israel
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Microparticles-Mediated Vascular Inflammation and its Amelioration by Antioxidant Activity of Baicalin. Antioxidants (Basel) 2020; 9:antiox9090890. [PMID: 32962240 PMCID: PMC7555600 DOI: 10.3390/antiox9090890] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 09/14/2020] [Accepted: 09/18/2020] [Indexed: 02/07/2023] Open
Abstract
Microparticles (MPs) are extracellular vesicles (0.1–1.0 μm in size), released in response to cell activation or apoptosis. Endothelial microparticles (EC-MP), vascular smooth muscle cell microparticles (VSMC-MP), and macrophage microparticles (MØ-MP) are key hallmarks of atherosclerosis progression. In our current study, we investigated the potent antioxidant activity of baicalin to ameliorate MP-induced vascular smooth muscle cell (VSMC) dysfunction and endothelial cell (EC) dysfunction, as well as the production of inflammatory mediators in macrophage (RAW264.7). In our study, baicalin suppressed the apoptosis, reactive oxygen species (ROS) generation, NO production, foam cell formation, protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in MØ-MP-induced RAW264.7. In addition, VSMC migration induced by VSMC-MP was dose-dependently inhibited by baicalin. Likewise, baicalin inhibits metalloproteinase-9 expression and suppresses VSMC-MP-induced VSMC proliferation by down-regulation of mitogen-activated protein kinase and proliferating cell nuclear antigen protein expressions. Baicalin also inhibited ROS production and apoptosis in VSMC. In EC, the marker of endothelial dysfunction (endothelial senescence, upregulation of ICAM, and ROS production) induced by EC-MP was halted by baicalin. Our results suggested that baicalin exerts potent biological activity to restore the function of EC and VSMC altered by their corresponding microparticles and inhibits the release of inflammation markers from activated macrophages.
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Badimon L, Suades R, Vilella-Figuerola A, Crespo J, Vilahur G, Escate R, Padro T, Chiva-Blanch G. Liquid Biopsies: Microvesicles in Cardiovascular Disease. Antioxid Redox Signal 2020; 33:645-662. [PMID: 31696726 DOI: 10.1089/ars.2019.7922] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Significance: Circulating microvesicles (cMV) are small (0.1-1 μm) phospholipid-rich blebs released by almost all cell types, and their release increases with cell activation and injury, thus reflecting the state of the cell from which they are originated. Microvesicles (MV) are found in the bloodstream, and they affect the phenotype of recipient cells, after local or systemic circulation, by intercellular transfer of their molecular content. Recent Advances: Several studies suggest the use of cell-specific MV subpopulations as predictive biomarkers for cardiovascular diseases (CVDs) at different stages and degrees of severity. In this review, we describe the state of the art of cMV as noninvasive surrogate biomarkers of vascular injury and dysfunction correlated with poor clinical outcomes in CVD. Critical Issues: Despite the growing body of evidence supporting the importance of cMV as hallmarks of CVD and their utility as biomarkers of CVD, the specific roles of each phenotype of cMV in CVD burden and prognosis still remain to be elucidated and validated in large cohorts. In addition, the development of standardized and reproducible techniques is required to be used as biomarkers for disease progression in the clinical setting. Future Directions: A multipanel approach with specific cMV phenotypes, added to current biomarkers and scores, will undoubtedly provide unique prognostic information to stratify patients for appropriate therapy on the basis of their risk of atherothrombotic disease and will open a new research area as therapeutic targets for CVD. MV will add to the implementation of precision medicine by helping the cellular and molecular characterization of CVD patients.
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Affiliation(s)
- Lina Badimon
- Cardiovascular Program ICCC, Institut de Recerca de l'Hospital Santa Creu i Sant Pau-IIB Sant Pau, Barcelona, Spain.,CIBER Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Rosa Suades
- Cardiovascular Program ICCC, Institut de Recerca de l'Hospital Santa Creu i Sant Pau-IIB Sant Pau, Barcelona, Spain.,Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Alba Vilella-Figuerola
- Cardiovascular Program ICCC, Institut de Recerca de l'Hospital Santa Creu i Sant Pau-IIB Sant Pau, Barcelona, Spain
| | - Javier Crespo
- Cardiovascular Program ICCC, Institut de Recerca de l'Hospital Santa Creu i Sant Pau-IIB Sant Pau, Barcelona, Spain
| | - Gemma Vilahur
- Cardiovascular Program ICCC, Institut de Recerca de l'Hospital Santa Creu i Sant Pau-IIB Sant Pau, Barcelona, Spain.,CIBER Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Rafael Escate
- Cardiovascular Program ICCC, Institut de Recerca de l'Hospital Santa Creu i Sant Pau-IIB Sant Pau, Barcelona, Spain.,CIBER Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Teresa Padro
- Cardiovascular Program ICCC, Institut de Recerca de l'Hospital Santa Creu i Sant Pau-IIB Sant Pau, Barcelona, Spain.,CIBER Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Gemma Chiva-Blanch
- Cardiovascular Program ICCC, Institut de Recerca de l'Hospital Santa Creu i Sant Pau-IIB Sant Pau, Barcelona, Spain
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Assessment of extracellular vesicles using IFC for application in transfusion medicine. Transfus Apher Sci 2020; 59:102942. [PMID: 32943325 DOI: 10.1016/j.transci.2020.102942] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Extracellular vesicles (EVs) have been shown to be involved in various physiological and pathophysiological processes. With respect to Transfusion Medicine, the accumulation of EVs in blood products during hypothermic storage is an indicator of the storage lesion and reportedly correlates with adverse effects after transfusion, including but not limited to immunomodulation, activation of coagulation, endothelial activation, and others. To optimally reduce such an impact on blood product quality degradation and improve post-transfusion outcomes, better methods for detection, enumeration, characterisation by size and phenotype, and functional involvement of EVs in different pathophysiological and physiological processes are required. Currently, Imaging Flow Cytometry (IFC) technology provides the most comprehensive assessment of EV subsets in different body fluids. The unique ability of IFC to detect EVs of 20 nm size by registration of a single pixel of fluorescence signal makes this approach highly promising for comprehensive studies of EVs. In this review, we will focus on the recent breakthrough and advantages of using the ImageStreamX MKII IFC platform for the detection and characterisation of EVs and its future prospects for routine application of IFC in Transfusion Medicine.
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Zhang S, Yin Y, Li C, Zhao Y, Wang Q, Zhang X. PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells. Aging (Albany NY) 2020; 12:12740-12749. [PMID: 32657762 PMCID: PMC7377857 DOI: 10.18632/aging.103173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 04/07/2020] [Indexed: 11/25/2022]
Abstract
Tumor necrosis factor-α (TNF) is a pro-inflammatory cytokine upregulated in many inflammatory diseases, and a potent inducer of endothelial cell-derived microparticle (EMP) formation. In this study, we identified the protein kinase PAK4 as a key regulator of the TNF-induced EMP release from human umbilical vein endothelial cells (HUVECs). TNF induces dose- and time-dependent EMP release and downregulation of PAK4 and upstream cdc42 in HUVECs. PAK4 suppression or inhibition of its kinase activity increases TNF-induced EMP release and apoptosis in HUVECs, while PAK4 overexpression reduces EMP release and apoptosis in TNF-stimulated cells. Collectively, these data indicate that PAK4 suppresses TNF-induced EMP generation occurring during apoptosis, and suggest that modulation of PAK4 activity may represent a novel approach to suppress the TNF-induced EMP levels in pro-inflammatory disorders and other pathological conditions.
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Affiliation(s)
- Shouqin Zhang
- Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Jing'an, Shanghai, China
| | - Yingjie Yin
- Department of Critical Care Medicine, The Affiliated Hospital of Medical School of Ningbo, Jiangbei District, Ningbo, Zhejiang Province, China
| | - Congye Li
- Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Jing'an, Shanghai, China
| | - Yi Zhao
- Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Jing'an, Shanghai, China
| | - Qixing Wang
- Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Jing'an, Shanghai, China
| | - Xiangyu Zhang
- Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Jing'an, Shanghai, China
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39
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Induction of erythrocyte microvesicles by Escherichia Coli Alpha hemolysin. Biochem J 2020; 476:3455-3473. [PMID: 31661116 DOI: 10.1042/bcj20190546] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 10/03/2019] [Accepted: 10/29/2019] [Indexed: 01/11/2023]
Abstract
Alpha hemolysin (HlyA) is the major virulence factor of uropathogenic Escherichia coli (UPEC) strains. Once in circulation, a low concentration of the toxin induces an increase in intracellular calcium that activates calpains - which proteolyse cytoskeleton proteins - and also favours the exposure of phosphatidylserine (PS) in the outer leaflet of erythrocyte membranes. All these events are considered part of eryptosis, as well as the delivery of microvesicles (MVs). Within this context, we studied the delivery of MVs by erythrocytes treated with sublytic concentrations of HlyA and demonstrated that HlyA-treated erythrocytes secrete MVs of diameter ∼200 nm containing HlyA and PS by a mechanism involving an increment of intracellular calcium concentration and purinergic receptor activation. Despite the presence of toxin in their membrane, HlyA-MVs are not hemolytically active and do not induce ATP release in untreated erythrocytes, thus suggesting that the delivery of HlyA-MVs might act as a protective mechanism on the part of erythrocytes that removes the toxin from the membrane to prevent the spread of infection. Although erythrocytes have been found to eliminate denatured hemoglobin and several membrane proteins by shedding MVs, the present work has revealed for the first time that an exogenous protein, such as a toxin, is eliminated by this process. This finding sheds light on the mechanism of action of the toxin and serves to further elucidate the consequences of UPEC infection in patients exhibiting HlyA-related diseases.
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40
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Elevated Microparticles, Thrombin-antithrombin and VEGF Levels in Colorectal Cancer Patients Undergoing Chemotherapy. Pathol Oncol Res 2020; 26:2499-2507. [PMID: 32583332 PMCID: PMC7471181 DOI: 10.1007/s12253-020-00854-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 06/11/2020] [Indexed: 12/11/2022]
Abstract
Hypercoagulable state and neoangiogenesis are common phenomena associated with malignancy. Cancer patients have increased levels of circulating endothelium-derived microparticles (EMPs), which have been hypothesized to be involved in numerous pathophysiological processes. Hemostasis and angiogenesis are also activated in colorectal cancer (CRC) patients. The study aimed to investigate potential influence of chemotherapy on EMPs, thrombin anti-thrombin complex (TAT) and vascular endothelial growth factor (VEGF) levels in CRC patients undergoing chemotherapy. The study group consisted of 18 CRC patients: 8 stage III colon cancer (CC) and 10 stage IV rectal cancer (RC) patients. EMPs, TAT and VEGF levels were assessed before chemotherapy and after the third course. Results were compared with 10 healthy subjects. EMP concentration was measured by flow cytometry, while TAT and VEGF concentrations were assayed employing ELISA. Compared to the control group, CC and RC patients had significantly higher levels of tissue factor (TF)-bearing and non-TF-bearing EMPs before and after three courses of chemotherapy. VEGF concentrations in CRC patients were higher than in the control groups and increased following chemotherapy. TAT levels were elevated in CRC patients before chemotherapy compared to healthy subjects and significantly increased after the third course of chemotherapy. No significant correlation was found either between EMP and TAT levels, or between EMP concentrations and VEGF levels in the study group. CRC patients have increased EMPs, and TAT as well as VEGF levels tend to increase during chemotherapy.
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41
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Lipets EN, Antonova OA, Shustova ON, Losenkova KV, Mazurov AV, Ataullakhanov FI. Use of Thrombodynamics for revealing the participation of platelet, erythrocyte, endothelial, and monocyte microparticles in coagulation activation and propagation. PLoS One 2020; 15:e0227932. [PMID: 32469873 PMCID: PMC7259734 DOI: 10.1371/journal.pone.0227932] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 05/13/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND AND OBJECTIVE For many pathological states, microparticles are supposed to be one of the causes of hypercoagulation. Although there are some indirect data about microparticles participation in coagulation activation and propagation, the integral hemostasis test Thrombodynamics allows to measure micropaticles participation in these two coagulation phases directly. Demonstrates microparticles participation in coagulation activation by influence on the appearance of coagulation centres in the plasma volume and the rate of clot growth from the surface with immobilized tissue factor.Methods: Microparticles were obtained from platelets and erythrocytes by stimulation with thrombin receptor-activating peptide (SFLLRN) and calcium ionophore (A23187), respectively, from monocytes, endothelial HUVEC culture and monocytic THP cell culture by stimulation with lipopolysaccharides. Microparticles were counted by flow cytometry and titrated in microparticle-depleted normal plasma in the Thrombodynamics test. RESULTS Monocyte microparticles induced the appearance of clotting centres through the TF pathway at concentrations approximately 100-fold lower than platelet and erythrocyte microparticles, which activated plasma by the contact pathway. For endothelial microparticles, both activation pathways were essential, and their activity was intermediate. Monocyte microparticles induced plasma clotting by the appearance of hundreds of clots with an extremely slow growth rate, while erythrocyte microparticles induced the appearance of a few clots with a growth rate similar to that from surface covered with high-density tissue factor. Patterns of clotting induced by platelet and endothelial microparticles were intermediate. Platelet, erythrocyte and endothelial microparticles impacts on the rate of clot growth from the surface with tissue factor did not differ significantly within the 0-200·103/ul range of microparticles concentrations. However, at concentrations greater than 500·103/ul, erythrocyte microparticles increased the stationary clot growth rate to significantly higher levels than do platelet microparticles or artificial phospholipid vesicles consisting of phosphatidylcholine and phosphatidylserine. CONCLUSION Microparticles of different origins demonstrated qualitatively different characteristics related to coagulation activation and propagation.
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Affiliation(s)
- E. N. Lipets
- Department of Biophysics, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
- Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russian Federation
| | - O. A. Antonova
- Institute of Experimental Cardiology, National Medical Research Center for Cardiology, Russian Ministry of Health, Moscow, Russian Federation
| | - O. N. Shustova
- Institute of Experimental Cardiology, National Medical Research Center for Cardiology, Russian Ministry of Health, Moscow, Russian Federation
| | - K. V. Losenkova
- Medicity Research Laboratory, University of Turku, Turku, Finland
| | - A. V. Mazurov
- Institute of Experimental Cardiology, National Medical Research Center for Cardiology, Russian Ministry of Health, Moscow, Russian Federation
| | - F. I. Ataullakhanov
- Department of Biophysics, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
- Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russian Federation
- Faculty of Physics, Lomonosov Moscow State University, Moscow, Russian Federation
- Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russian Federation
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Taylor J, Azimi I, Monteith G, Bebawy M. Ca 2+ mediates extracellular vesicle biogenesis through alternate pathways in malignancy. J Extracell Vesicles 2020; 9:1734326. [PMID: 32194926 PMCID: PMC7067202 DOI: 10.1080/20013078.2020.1734326] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 01/30/2020] [Accepted: 02/11/2020] [Indexed: 12/28/2022] Open
Abstract
Extracellular vesicles (EVs) are small membrane vesicles that serve as important intercellular signalling intermediaries in both malignant and non-malignant cells. For EVs formed by the plasma membrane, their biogenesis is characterized by an increase in intracellular calcium followed by successive membrane and cytoskeletal changes. EV-production is significantly higher in malignant cells relative to non-malignant cells and previous work suggests this is dependent on increased calcium mobilization and activity of calpain. However, calcium-signalling pathways involved in malignant and non-malignant EV biogenesis remain unexplored. Here we demonstrate; malignant cells have high basal production of plasma membrane EVs compared to non-malignant cells and this is driven by a calcium–calpain dependent pathway. Resting vesiculation in malignant cells occurs via mobilization of calcium from endoplasmic reticulum (ER) stores rather than from the activity of plasma membrane calcium channels. In the event of ER store depletion however, the store-operated calcium entry (SOCE) pathway is activated to restore ER calcium stores. Depleting both ER calcium stores and blocking SOCE, inhibits EV biogenesis. In contrast, calcium signalling pathways are not activated in resting non-malignant cells. Consequently, these cells are relatively low vesiculators in the resting state. Following cellular activation however, an increase in cytosolic calcium and activation of calpain increase in EV biogenesis. These findings contribute to furthering our understanding of extracellular vesicle biogenesis. As EVs are key mediators in the intercellular transfer of deleterious cancer traits such as cancer multidrug resistance (MDR), understanding the molecular mechanisms governing their biogenesis in cancer is the crucial first step in finding novel therapeutic targets that circumvent EV-mediated MDR.
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Affiliation(s)
- Jack Taylor
- Discipline of Pharmacy, Graduate School of Health, The University of Technology Sydney, Australia
| | - Iman Azimi
- Division of Pharmacy, College of Health and Medicine, University of Tasmania, Australia
| | - Gregory Monteith
- School of Pharmacy, The University of Queensland, Brisbane, Australia.,Mater Research, Translational Research Institute, the University of Queensland, Brisbane, Australia.,Translational Research Institute, The University of Queensland, Brisbane, Australia
| | - Mary Bebawy
- Discipline of Pharmacy, Graduate School of Health, The University of Technology Sydney, Australia
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Čolić J, Matucci Cerinic M, Guiducci S, Damjanov N. Microparticles in systemic sclerosis, targets or tools to control fibrosis: This is the question! JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2020; 5:6-20. [PMID: 35382401 PMCID: PMC8922594 DOI: 10.1177/2397198319857356] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 05/20/2019] [Indexed: 07/25/2023]
Abstract
Systemic sclerosis is the main systemic fibrotic disease with unknown etiology characterized by peripheral microvascular injury, activation of immune system, and wide-spread progressive fibrosis. Microparticles can be derived from any cell type during normal cellular differentiation, senescence, and apoptosis, and also upon cellular activation. Carrying along a broad range of surface cytoplasmic and nuclear molecules of originating cells, microparticles are closely implicated in inflammation, thrombosis, angiogenesis, and immunopathogenesis. Recently, microparticles have been proposed as biomarkers of endothelial injury, which is the primary event in the genesis of tissue fibrosis. Microparticles may have a role in fostering endothelial to mesenchymal transition, thus giving a significant contribution to the development of myofibroblasts, the most important final effectors responsible for tissue fibrosis and fibroproliferative vasculopathy. Thanks to potent profibrotic mediators, such as transforming growth factor beta, platelet-derived growth factor, high mobility group box 1 protein, nicotinamide adenine dinucleotide phosphate oxidase 4, and antifibrotic agents, such as matrix metalloproteinases, microparticles may play an opposite role in fibrosis.
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Affiliation(s)
- Jelena Čolić
- Department of Rheumatology, Institute of
Rheumatology, Belgrade, Serbia
| | - Marco Matucci Cerinic
- Division of Rheumatology, Department of
Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi (AOUC)
and Denothe Centre, University of Florence, Florence, Italy
| | - Serena Guiducci
- Division of Rheumatology, Department of
Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi (AOUC)
and Denothe Centre, University of Florence, Florence, Italy
| | - Nemanja Damjanov
- Department of Rheumatology, Institute of
Rheumatology, Belgrade, Serbia
- School of Medicine, University of
Belgrade, Belgrade, Serbia
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44
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Thrombocytopenia and Coronary Artery Disease, the Existing Dilemmas. JOURNAL OF CARDIOVASCULAR EMERGENCIES 2019. [DOI: 10.2478/jce-2019-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
Background: Platelets play a pivotal role in the pathogenesis of acute coronary syndrome (ACS) and acute or chronic complications following percutaneous coronary intervention (PCI) as well. Platelet inhibition is a cornerstone treatment in the management of these patients. Thrombocytopenia in patients with ACS is uncommon. Idiopathic thrombocytopenic purpura (ITP) is a rare phenomenon; nevertheless, some case series presenting concomitant ACS and ITP have been described in the literature. The safety of antiplatelet therapy and PCI in patients who have ACS and thrombocytopenia is limited.
Case summary: We present a case of a 60-year-old patient with ITP who was admitted with unstable angina pectoris. On admission, the platelet count was 23 × 109/L. Coronary CT angiography revealed severe stenosis in the mid portion of RCA. After one-week treatment with high-dose Prednisolone, the platelet count recovered, and coronary catheterization was performed. Successful PCI to the RCA with drug-eluting stent was performed. The patient was discharged on dual antiplatelet therapy.
Conclusion: The case suggests that PCI is a suitable treatment for ITP patients with ACS. Hemostasis is the major concern in managing these patients. The treatment strategy may be based on platelet function rather than platelet count alone. Further analysis of antiplatelet therapies as mono or dual therapy are needed.
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45
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Guo J, Feng C, Zhang B, Zhang S, Shen X, Zhu J, Zhao XX. Extraction and identification of platelet‑derived microparticles. Mol Med Rep 2019; 20:2916-2921. [PMID: 31322221 DOI: 10.3892/mmr.2019.10484] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Accepted: 06/07/2019] [Indexed: 11/06/2022] Open
Abstract
Microparticles are carriers of signals for intracellular signal transduction. These carriers include proteins, mRNAs, microRNAs and other bioactive substances. Platelets are a major source of circulating microparticles, and microparticles are closely associated with the development of certain cardiovascular diseases. In the present study, a method for separating, extracting and identifying platelet‑derived microparticles was developed and differences in the expression of surface proteins on microparticles harvested from platelets stimulated by vortexing or treatment with thrombin was investigated. The counts, composition, sizes and inner structures of microparticles were determined using flow cytometry and transmission electron microscopy. Additionally, it was demonstrated that platelets could be readily activated, and a large quantity of microparticles with varying complex compositions, structures and sizes were derived from activated platelets. High purity platelet‑derived microparticles were obtained by gradient centrifugation. However, the microparticles derived from platelets stimulated by thrombin treatment or vortexing differed significantly in the levels of CD63. The present study aimed to provide improved options for the extraction and identification of microparticles.
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Affiliation(s)
- Jun Guo
- Department of Geriatrics, Anhui Provincial Hospital, Hefei, Anhui 230000, P.R. China
| | - Can Feng
- Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200433, P.R. China
| | - Bili Zhang
- Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China
| | - Shiyang Zhang
- Department of Geriatrics, Anhui Provincial Hospital, Hefei, Anhui 230000, P.R. China
| | - Xiaxian Shen
- Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China
| | - Jiaqi Zhu
- Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China
| | - Xian-Xian Zhao
- Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China
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van Manen L, Peters AL, van der Sluijs PM, Nieuwland R, van Bruggen R, Juffermans NP. Clearance and phenotype of extracellular vesicles after red blood cell transfusion in a human endotoxemia model. Transfus Apher Sci 2019; 58:508-511. [PMID: 31253560 DOI: 10.1016/j.transci.2019.05.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 05/21/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND In the critically ill, extracellular vesicles (EV) from red blood cells (RBC) have been related to adverse effects of blood transfusion. Stored RBC units contain high concentrations of RBC- EVs, thereby increasing the concentration of EVs in the circulation after transfusion. The mechanisms underlying the clearance of donor RBC-EVs after transfusion are unknown. This study investigates whether membrane markers that are associated with clearance of RBCs are also implicated in clearance of RBC-EVs in human endotoxemic recipients of a transfusion. METHODS Six volunteers were injected with Escherichia coli lipopolysaccharide, and after two hours transfused with an autologous RBC unit donated 35 days earlier. Samples were collected from the RBC unit and the volunteers before and after transfusion. RBC-EVs were labeled with (anti) glycophorin A, combined with (anti) CD44, CD47, CD55, CD59, CD147, or lactadherin to detect phosphatidylserine (PS) and analyzed on a A50 Micro flow cytometer. RESULTS In the RBC unit, RBC-EVs solely exposed PS (7.8%). Before transfusion, circulating RBC-EVs mainly exposed PS (22%) and CD59 (9.1%), the expression of the other membrane markers was much lower. After transfusion, the concentration of RBC- EVs increased 2.4-fold in two hours. Thereafter, the EV concentration decreased towards baseline levels. The fraction of EVs positive for all tested membrane markers decreased after transfusion. CONCLUSION Besides a minor fraction of PS-exposing EVs, RBC-EVs produced during storage do not expose detectable levels of RBC membrane markers that are associated with clearance, which is in contrast to the EVs produced by the circulating RBCs.
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Affiliation(s)
- Lisa van Manen
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Blood Cell Research, Sanquin research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
| | - Anna L Peters
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - P Matthijs van der Sluijs
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Rienk Nieuwland
- Laboratory of Experimental Clinical Chemistry, and Vesicle Observation Center, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Robin van Bruggen
- Department of Blood Cell Research, Sanquin research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Nicole P Juffermans
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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47
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Suzuki H. Inflammation: a Good Research Target to Improve Outcomes of Poor-Grade Subarachnoid Hemorrhage. Transl Stroke Res 2019; 10:597-600. [PMID: 31214920 DOI: 10.1007/s12975-019-00713-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 06/06/2019] [Accepted: 06/11/2019] [Indexed: 12/18/2022]
Affiliation(s)
- Hidenori Suzuki
- Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
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48
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Zahran AM, Mohamed IL, El Asheer OM, Tamer DM, Abo-ELela MGM, Abdel-Rahim MH, El-Badawy OHB, Elsayh KI. Circulating Endothelial Cells, Circulating Endothelial Progenitor Cells, and Circulating Microparticles in Type 1 Diabetes Mellitus. Clin Appl Thromb Hemost 2019; 25:1076029618825311. [PMID: 30760002 PMCID: PMC6714921 DOI: 10.1177/1076029618825311] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background and Aim: Hyperglycemia in type 1 diabetes (T1D) is accompanied by endothelial cell dysfunction
which is known to contribute to the pathogenesis of cardiovascular disorders. The aim of
the current study was to explore the profile of circulating endothelial progenitor cells
(EPCs), circulating endothelial cells (CECs), endothelial and platelet derived
micropaticles (EMPs, PMPs) and total microparticles (TMPs), in T1D children in relation
to each other and to the metabolic disorders accompanying T1D. Patients and Methods: Thirty T1D patients and 20 age and sex matched healthy volunteers were assessed for
HbA1c level and lipid profile. Quantification of CECs, EPCs, TMPs, EMPs and PMPs was
done by flow cytometry. Results: The mean levels of EMPs, PMPs, TMPs and CECs were significantly higher in diabetic
children compared to controls. Meanwhile, the levels of EPCs were significantly lower in
diabetic children compared to controls. Both PMPs and CECs showed the highest
significant differences between patients and controls and their levels were directly
related to HbA1c, total cholesterol, LDL and triglycerides. A moderate correlation was
observed between the frequency of PMPs and CECs. EPCs revealed negative correlations
with both LDL and triglycerides. TMPs were only related to LDL, while EMPs were only
related to HbA1c. Conclusion: Although there is disturbance in the levels of EMPs, PMPs, TMPs, CECs and EPCs in type
1 diabetic children compared to the controls, only the levels of PMPs and CECs were
closely affected by the poor glycemic control and dyslipidemia occurring in T1D; thus
may contribute to a higher risk of cardiovascular diseases.
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Affiliation(s)
- Asmaa M Zahran
- 1 Department of Clinical Pathology, South Egypt Cancer Institute, Assiut, Egypt
| | - Ismail L Mohamed
- 2 Pediatric Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Osama M El Asheer
- 2 Pediatric Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Deiaaeldin M Tamer
- 2 Pediatric Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | | | - Mona H Abdel-Rahim
- 3 Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Omnia H B El-Badawy
- 3 Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Khalid I Elsayh
- 2 Pediatric Department, Faculty of Medicine, Assiut University, Assiut, Egypt
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Sluijter JPG, Davidson SM, Boulanger CM, Buzás EI, de Kleijn DPV, Engel FB, Giricz Z, Hausenloy DJ, Kishore R, Lecour S, Leor J, Madonna R, Perrino C, Prunier F, Sahoo S, Schiffelers RM, Schulz R, Van Laake LW, Ytrehus K, Ferdinandy P. Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res 2019; 114:19-34. [PMID: 29106545 PMCID: PMC5852624 DOI: 10.1093/cvr/cvx211] [Citation(s) in RCA: 269] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 11/01/2017] [Indexed: 12/13/2022] Open
Abstract
Extracellular vesicles (EVs)—particularly exosomes and microvesicles (MVs)—are attracting considerable interest in the cardiovascular field as the wide range of their functions is recognized. These capabilities include transporting regulatory molecules including different RNA species, lipids, and proteins through the extracellular space including blood and delivering these cargos to recipient cells to modify cellular activity. EVs powerfully stimulate angiogenesis, and can protect the heart against myocardial infarction. They also appear to mediate some of the paracrine effects of cells, and have therefore been proposed as a potential alternative to cell-based regenerative therapies. Moreover, EVs of different sources may be useful biomarkers of cardiovascular disease identities. However, the methods used for the detection and isolation of EVs have several limitations and vary widely between studies, leading to uncertainties regarding the exact population of EVs studied and how to interpret the data. The number of publications in the exosome and MV field has been increasing exponentially in recent years and, therefore, in this ESC Working Group Position Paper, the overall objective is to provide a set of recommendations for the analysis and translational application of EVs focussing on the diagnosis and therapy of the ischaemic heart. This should help to ensure that the data from emerging studies are robust and repeatable, and optimize the pathway towards the diagnostic and therapeutic use of EVs in clinical studies for patient benefit.
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Affiliation(s)
- Joost Petrus Gerardus Sluijter
- Experimental Cardiology Laboratory, UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, University Utrecht, 3508GA Utrecht, The Netherlands
| | | | | | - Edit Iren Buzás
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.,MTA-SE Immunoproteogenomics Research Group, Budapest, Hungary
| | - Dominique Paschalis Victor de Kleijn
- Department of Vascular Surgery, UMC Utrecht, Utrecht University, Utrecht, the Netherlands.,Netherlands Heart Institute, Utrecht, the Netherlands
| | - Felix Benedikt Engel
- Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Zoltán Giricz
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
| | - Derek J Hausenloy
- Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857.,National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore 169609.,Yong Loo Lin School of Medicine, National University Singapore, 1E Kent Ridge Road, Singapore 119228.,The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London WC1E 6HX, UK.,The National Institute of Health Research University College London Hospitals Biomedical Research Centre, Research & Development, Maple House 1st floor, 149 Tottenham Court Road, London W1T 7DN, UK.,Department of Cardiology, Barts Heart Centre, St Bartholomew's Hospital, W Smithfield, London EC1A 7BE, UK
| | - Raj Kishore
- Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Sandrine Lecour
- Hatter Institute for Cardiovascular Research in Africa and Lionel Opie Preclinical Imaging Core Facility, Faculty of Health Sciences, University of Cape Town, South Africa
| | - Jonathan Leor
- Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel Hashomer, Israel; Tamman Cardiovascular Research Institute, Heart Center, Sheba Medical Center, Tel Hashomer, Israel
| | - Rosalinda Madonna
- Center of Aging Science and Regenerative Medicine, CESI-Met and Institute of Cardiology, "G. D'Annunzio" University, Chieti-Pescara, Chieti, Italy.,Department of Internal Medicine, University of Texas Medical School in Houston, TX, USA.,Texas Heart Institute, Houston, TX, USA
| | - Cinzia Perrino
- Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Fabrice Prunier
- Institut Mitovasc, CHU d'Angers, Université d'Angers, Angers, France
| | - Susmita Sahoo
- Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ray Michel Schiffelers
- Laboratory Clinical Chemistry and Hematology Division, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Rainer Schulz
- Institute of Physiology, Justus-Liebig University of Giessen, Aulweg 129, 35392, Giessen, Germany
| | - Linda Wilhelmina Van Laake
- Division Heart and Lungs, and Hubrecht Institute, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Kirsti Ytrehus
- Cardiovascular Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
| | - Péter Ferdinandy
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest 1089, Hungary and.,Pharmahungary Group, Szeged, Hungary
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50
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Zhong WQ, Ren JG, Xiong XP, Man QW, Zhang W, Gao L, Li C, Liu B, Sun ZJ, Jia J, Zhang WF, Zhao YF, Chen G. Increased salivary microvesicles are associated with the prognosis of patients with oral squamous cell carcinoma. J Cell Mol Med 2019; 23:4054-4062. [PMID: 30907490 PMCID: PMC6533497 DOI: 10.1111/jcmm.14291] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 12/17/2018] [Accepted: 03/08/2019] [Indexed: 01/08/2023] Open
Abstract
Microvesicles (MVs), which are cell-derived membrane vesicles present in body fluids, are closely associated with the development of malignant tumours. Saliva, one of the most versatile body fluids, is an important source of MVs. However, the association between salivary MVs (SMVs) and oral squamous cell carcinoma (OSCC), which is directly immersed in the salivary milieu, remains unclear. SMVs from 65 patients with OSCC, 21 patients with oral ulcer (OU), and 42 healthy donors were purified, quantified and analysed for their correlations with the clinicopathologic features and prognosis of OSCC patients. The results showed that the level of SMVs was significantly elevated in patients with OSCC compared to healthy donors and OU patients. Meanwhile, the level of SMVs showed close correlations with the lymph node status, and the clinical stage of OSCC patients. Additionally, the ratio of apoptotic to non-apoptotic SMVs was significantly decreased in OSCC patients with higher pathological grade. Consistently, poorer overall survival was observed in patients with lower ratio of apoptotic to non-apoptotic SMVs. In conclusion, the elevated level of SMVs is associated with clinicopathologic features and decreased survival in patients with OSCC, suggesting that SMVs are a potential biomarker and/or regulator of the malignant progression of OSCC.
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Affiliation(s)
- Wen-Qun Zhong
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.,Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Jian-Gang Ren
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.,Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Xue-Peng Xiong
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.,Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Qi-Wen Man
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Wei Zhang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.,Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Lu Gao
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Chen Li
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Bing Liu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.,Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zhi-Jun Sun
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.,Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Jun Jia
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Wen-Feng Zhang
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Yi-Fang Zhao
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Gang Chen
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.,Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
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