• Dengue
• Matrix Metalloproteinases
• PECAM-1
• Plasma Leakage
• Thrombocytopenia

• Humans
• Male
• Dengue/blood
• Dengue/diagnosis
• Female
• Matrix Metalloproteinase 14/blood
• Platelet Endothelial Cell Adhesion Molecule-1/blood
• Biomarkers/blood
• Adult
• Severity of Illness Index
• Middle Aged
• Young Adult
• Severe Dengue/blood
• Severe Dengue/diagnosis
• Case-Control Studies
• Adolescent

• Humans
• Blood Platelets/metabolism
• Neurodegenerative Diseases/immunology
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/pathology
• Animals
• Alzheimer Disease/metabolism
• Alzheimer Disease/immunology
• Alzheimer Disease/pathology
• Inflammation/metabolism
• Inflammation/immunology

• 23A12 The Florida Department of Health
• AARG-22-974437 Alzheimer's Association
• R21AG075798 NIA NIH HHS
• R21AG082193 NIA NIH HHS

• Metabolic syndrome
• follistatin
• platelet/endothelial cell adhesion molecule-1
• pregnancy-associated plasma protein-A

• Male
• Female
• Humans
• Adolescent
• Metabolic Syndrome/complications
• Cardiovascular Diseases/etiology
• Platelet Endothelial Cell Adhesion Molecule-1/metabolism
• Follistatin
• Diabetes Mellitus, Type 2/complications
• Biomarkers
• Risk Factors
• Pregnancy-Associated Plasma Protein-A/analysis
• Pregnancy-Associated Plasma Protein-A/metabolism
• Heart Disease Risk Factors

• Alzheimer's disease (AD)
• CD31
• blood–brain barrier (BBB)
• neuroinflammation
• trans-endothelia

• Humans
• Alzheimer Disease/metabolism
• Blood-Brain Barrier/metabolism
• Platelet Endothelial Cell Adhesion Molecule-1/genetics
• Platelet Endothelial Cell Adhesion Molecule-1/metabolism
• Signal Transduction
• Transendothelial and Transepithelial Migration

• R01 AI054546 NIAID NIH HHS

• Angiogenesis
• Diabetic retinopathy
• Inflammation
• Neurodegeneration
• Tocotrienol-rich fraction

• 600-IRMI/FRGS 5/3 (101/2019) Ministry of Higher Education, Malaysia
• 600-IRMI/FRGS 5/3 (101/2019) Ministry of Higher Education, Malaysia
• 600-IRMI/FRGS 5/3 (101/2019) Ministry of Higher Education, Malaysia

• allotransplantation
• scientific data
• statistics

During viral-induced myocarditis, immune cells migrate towards the site of infection and secrete proteases, which in turn can act as sheddases by cleaving extracellular domains of transmembrane proteins. We were interested in the shedding of the Coxsackie- and adenovirus receptor (CAR) that acts as an entry receptor for both eponymous viruses, which cause myocarditis. CAR shedding by secreted immune proteases could result in a favourable outcome of myocarditis as CAR’s extracellular domain would be removed from the cardiomyocytes’ surface leading to decreased susceptibility to ongoing viral infections.

In this work, matrix metalloproteinases and serine proteinases were screened for their proteolytic activity towards human CAR. Whereas matrix metalloproteinases, proteinase 3, and cathepsin G did not cleave human recombinant CAR or only within long incubation times, neutrophil elastase showed a distinct cleavage pattern of CAR’s extracellular domain that was time- and dose-dependent. Neutrophil elastase cleaves CAR at its membrane-proximal immunoglobulin domain as we determined by nanoLC-MS/MS. Furthermore, neutrophil elastase treatment of cells reduced CAR surface levels as seen by flow cytometry and immunofluorescence microscopy.

With this study, we show that CAR might be a target for shedding by neutrophil elastase.

The online version contains supplementary material available at 10.1007/s11033-022-07153-2.

• IFN-γ
• PECAM-1
• TNF-α
• diabetic retinopathy
• ubiquitination

Immune responses of fetal membranes involve the production of chemoattractant mediators causing infiltration of maternal and fetal leukocytes, intrauterine inflammation and potentially the disruption of maternal‐fetal tolerance. Prolactin (PRL) has deep immunoregulatory effects in the fetal‐maternal interface. We aimed to test the in vitro PRL effect upon chemotactic capacities of human fetal membranes.

Fetal membranes and umbilical cord blood were collected from healthy non‐laboring caesarean deliveries at term. Fetal membranes were cultured in Transwell® frames to mimic the barrier function between choriodecidual and amniotic sides. Tissues were treated with PRL, Lipopolysaccharide (LPS), or both simultaneously. Then, RANTES, MCP‐1, MIP‐1α, IP‐10, and PECAM‐1 were quantified in a conditioned medium by choriodecidual or amniotic sides. The chemotaxis of subsets of migrating mononuclear cells from umbilical cord blood was evaluated in a Boyden Chamber in response to the conditioned medium by both sides.

Lipopolysaccharide stimulates the production of RANTES, MCP‐1, MIP‐1α, and PECAM‐1 in choriodecidua, while MIP‐1α and PECAM‐1 only increase in amnion. PRL decrease RANTES, MCP‐1, and MIP‐1 only in choriodecidua, but PECAM‐1 was decreased mainly in amnion. The leukocyte migration was regulated significantly in response to the conditioned medium by the amnion, increase in the conditioned medium after LPS treatment, contrary with, the leukocyte migration decreased in a significant manner in response to conditioned medium after PRL and LPS‐PRL co‐treatment. Finally, T cells were the most responsive subset of cells.

Prolactin modified in a tissue‐specific manner the chemotactic factor and the leukocyte migration differentially in fetal membranes.

• LPS
• T cells
• amnion
• leukocytes
• migration
• prolactin

Microvessel hypoperfusion following ischemic stress resulted in a decreased shear stress of brain microvascular endothelial cells (BMECs) and contributed to abnormal expression of PECAM-1 after global cerebral ischemia/reperfusion (I/R) injury. Here, we identified novel pathophysiologic and rehabilitative procedures specific to shear stress in microvascular endothelial cells in response to global cerebral I/R injury. We found that the decrease in cerebral blood flow of gerbils after global cerebral I/R injury reduces shear stress, and the abnormal change in shear stress leads to microvascular endothelial cell and neuron damage. Nevertheless, suitable high levels of shear stress contribute to rescuing the dysfunction and malformation of BMECs via regulating the PECAM-1-eNOS-NO pathway to enhance nitric oxide release, decrease the expression of caspase-3 to reduce apoptosis, and improve the shear-adaptability of endothelial cells, thereby playing a protective role in the gerbil brain.

• PECAM-1
• brain microvascular endothelial cells
• global cerebral ischemia reperfusion injury
• nitric oxide
• shear stress

• Adhesion molecules
• Multiple sclerosis
• Rehabilitative exercise
• Selectins
• VAP-1

• Adult
• Biomarkers/blood
• Cell Adhesion Molecules/blood
• Female
• Humans
• Male
• Middle Aged
• Multiple Sclerosis, Chronic Progressive/blood
• Multiple Sclerosis, Chronic Progressive/rehabilitation
• Recovery of Function/physiology
• Rehabilitation/methods
• Robotics

Neurodegenerative diseases are characterized by neuronal degeneration as well as neuroinflammation. While CD38 is strongly expressed in brain cells including neurons, astrocytes as well as microglial cells, the role played by CD38 in neurodegeneration and neuroinflammation remains elusive. Yet, CD38 expression increases as a consequence of aging which is otherwise the primary risk associated with neurodegenerative diseases, and several experimental data demonstrated that CD38 knockout mice are protected from neurodegenerative and neuroinflammatory insults. Moreover, nicotinamide adenine dinucleotide, whose levels are tightly controlled by CD38, is a recognized and potent neuroprotective agent, and NAD supplementation was found to be beneficial against neurodegenerative diseases. The aims of this review are to summarize the physiological role played by CD38 in the brain, present the arguments indicating the involvement of CD38 in neurodegeneration and neuroinflammation, and to discuss these observations in light of CD38 complex biology.

• ALS.
• Alzheimer’s disease
• CD38
• NAD
• Parkinson’s disease
• aging
• neurodegeneration
• neuroinflammation

• Endothelium
• Glycocalyx
• Matrix metalloproteinases
• Methamphetamine

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that leads to the death of neurons and oligodendrocytes, which cannot be measured in living subjects. Physiological cellular death, otherwise known as apoptosis, progresses through a series of stages which culminates in the discharge of cellular contents into vesicles known as apoptotic bodies (ABs) or apoptosomes. These ABs can be detected in bodily fluids as Annexin-V-positive vesicles of 0.5–4.0 μm in size. In addition, the origin of these ABs might be detected by staining for cell-specific surface markers. Thus, we investigated whether quantifications of the total and CNS cell-specific ABs in the cerebrospinal fluid (CSF) of patients provided any clinical value in MS. Extracellular vesicles, from CSF of 64 prospectively-acquired subjects, were collected in a blinded fashion using ultra-centrifugation. ABs were detected by flow cytometry using bead-enabled size-gating and Annexin-V-staining. The origin of these ABs was further classified by staining the vesicles for cell-specific surface markers. Upon unblinding, we evaluated the differences between diagnostic categories and correlations with clinical measures. There were no statistically significant differences in the numbers of total or any cell-specific ABs across different disease diagnostic subgroups and no significant correlations with any of the tested clinical measures of CNS tissue destruction, disability, MS activity, and severity (i.e., rates of disability accumulation). Overlap of cell surface markers suggests inability to reliably determine origin of ABs using antibody-based flow cytometry. These negative data suggest that CNS cells in MS either die by non-apoptotic mechanisms or die in frequencies indistinguishable by current assays from apoptosis of other cells, such as immune cells performing immunosurveillance in healthy conditions.

• apoptotic bodies
• cell surface markers
• cerebrospinal fluid
• clinical outcomes
• flow cytometry
• multiple sclerosis

Hypobaric hypoxia has been reported to cause endothelial cell and platelet dysfunction implicated in the formation of microvascular lesions, and in its extremes may contribute to vascular leakage in high altitude pulmonary edema or blood brain barrier disruption leading to cerebral micro-hemorrhage (MH). Platelet function in the development of microvascular lesions remained ill defined, and is still incompletely understood. In this study platelet- and endothelial cell-derived extracellular vesicles (PEV and EEV, respectively) and cell adhesion molecules were characterized in plasma samples of members of a high altitude expedition to delineate the contribution of platelets and endothelial cells to hypobaric hypoxia-induced vascular dysfunction.

In this observational study, platelet and endothelial cell-derived extracellular vesicles were analysed by flow-cytometry in plasma samples from 39 mountaineers participating in a medical research climbing expedition to Himlung Himal, Nepal, 7,050m asl. Megakaryocyte/platelet-derived AnnexinV^pos, PECAM-1 (CD31) and glycoprotein-1b (GP1b, CD42b) positive extracellular vesicles (PEV) constituted the predominant fraction of EV in plasma samples up to 6,050m asl. Exposure to an altitude of 7,050m led to a marked decline of CD31^pos CD42^neg EEV as well as of CD31^pos CD42b^pos PEV at the same time giving rise to a quantitatively prevailing CD31^neg CD42b^low/neg subpopulation of AnnexinV^pos EV. An almost hundredfold increase in the numbers of this previously unrecognized population of CD31^neg CD42b^low/neg EV was observed in all participants reaching 7,050m asl.

The emergence of CD31^neg CD42b^low/neg EV was observed in all participants and thus represents an early hypoxic marker at extreme altitude. Since CD31 and CD42b are required for platelet-endothelial cell interactions, these hypobaric hypoxia-dependent quantitative and phenotypic changes of AnnexinV^pos EV subpopulations may serve as early and sensitive indicators of compromised vascular homeostasis.

• Acclimatization
• Altitude
• Annexin A5/blood
• Endothelial Cells/metabolism
• Endothelial Cells/pathology
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/pathology
• Humans
• Hypoxia/physiopathology
• Middle Aged
• Platelet Endothelial Cell Adhesion Molecule-1/blood

• endothelial injury
• mechanical ventilation
• platelet-endothelial cell adhesion molecule
• pulmonary fibrosis
• ventilator-induced lung injury
• wingless-related integration site

• Humans
• Lung/physiology
• Lung Injury/immunology
• Lung Injury/metabolism
• Lung Injury/pathology
• Platelet Endothelial Cell Adhesion Molecule-1/metabolism
• Pulmonary Fibrosis/metabolism
• Regeneration
• Respiratory Distress Syndrome/metabolism
• Respiratory Distress Syndrome/pathology
• Respiratory Distress Syndrome/physiopathology
• Wnt Signaling Pathway/physiology

• FDN143285 CIHR

• Blood-retinal barrier
• Diabetes
• Oxidative stress
• Permeability
• Retina

• R01 EY025632 NEI NIH HHS

• endothelial cell
• microcirculation
• molecular biology
• pulmonary arterial hypertension
• shear stress

• adhesion molecule
• blood vessel
• endothelial cell
• inflammation
• vascular permeability

• allergic airway inflammation
• apoptosis
• eosinophils
• galectin-1
• migration

• endothelium
• immunology
• inflammation
• lymphocytes
• transplantation

• Endothelial Microparticles
• Ischemic Cerebrovascular Diseases
• Stoke

• Cadherins/metabolism
• Cell-Derived Microparticles
• Cerebrovascular Disorders/immunology
• Cerebrovascular Disorders/mortality
• Endothelial Cells/metabolism
• Humans
• Middle Aged
• Stroke/mortality

• Autoimmune arthritis
• CD31
• ITIM
• Immunological synapse
• Inhibitory receptors
• T lymphocytes

Recently, we reported the properties of CD31-expressing cells in healthy individuals. However, the characteristics of CD31-expressing cells derived from coronary artery disease (CAD) patients remain unknown. This study aimed to investigate the relationship between circulating CD31⁺ cells and CAD as well as their biological characteristics. Analysis with flow cytometry revealed that CD31⁺ cells (C-CD31) from the peripheral blood (PB) of CAD patients exhibited low levels of T-cell marker and high levels of macrophage marker compared with the PB-CD31⁺ cells from healthy individuals (H-CD31). In addition, the expression levels of multiple pro-angiogenic and chemokine genes were significantly down-regulated in C-CD31. However, inflammatory gene IL-1α was highly up-regulated in C-CD31. Patients with unstable angina (UA) had significantly more CD31⁺ cells in the PB than healthy control group (P < 0.001). Moreover, there were significant correlations between the number of CD31⁺ cells and cardiovascular (CV) disease activity (R = 0.318, P = 0.006) and the number of diseased coronaries (R = 0.312, P = 0.005). For the diagnostic category of UA, the area under curve was 0.803 (P < 0.001). In conclusion, C-CD31 have impaired angiogenic potential and the number of circulating CD31⁺ cells were correlated with CV risk. These findings may contribute to the understanding of the pathogenesis of CAD.

• CD31 antigen
• angina pectoris
• angiogenesis effect
• coronary artery disease
• inflammation

Tissue contacting surfaces of medical devices initiate a host inflammatory response, characterized by adsorption of blood proteins and inflammatory cells triggering the release of cytokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS), in an attempt to clear or isolate the foreign object from the body. This normal host response contributes to device-associated pathophysiology and addressing device biocompatibility remains an unmet need. Although widespread attempts have been made to render the device surfaces unreactive, the establishment of a completely bioinert coating has been untenable and demonstrates the need to develop strategies based upon the molecular mechanisms that define the interaction between host cells and synthetic surfaces. In this review, we discuss a family of transmembrane receptors, known as immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors, which show promise as potential targets to address aberrant biocompatibility. These receptors repress the immune response and ensure that the intensity of an immune response is appropriate for the stimuli. Particular emphasis will be placed on the known ITIM-containing receptor, Signal Regulatory Protein Alpha (SIRPhα), and its cognate ligand CD47. In addition, this review will discuss the potential of other ITIM-containing proteins as targets for addressing the aberrant biocompatibility of polymeric biomaterials.

• CD200R
• CD47
• PECAM-1
• SIRPα
• immunoreceptor tyrosine-based inhibitory motif (ITIM)

The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.

• Gastrointestinal cancer
• Matrix metalloproteinase
• Tissue inhibitor of matrix metalloproteinases
• Reactive oxygen species
• Antioxidants

• drug targeting
• intracellular delivery
• nanoparticles
• nanomedicine
• nanocarriers
• endothelium
• cell adhesion molecules
• icam-1
• ace
• pecam

• Animals
• Binding Sites
• Cell Adhesion Molecules/physiology
• Drug Delivery Systems
• Endothelium, Vascular/drug effects
• Enzymes/physiology
• Humans
• Hydrodynamics
• Intercellular Adhesion Molecule-1/physiology
• Ligands
• Nanomedicine/methods
• Nanoparticles/chemistry
• Phenotype
• Platelet Endothelial Cell Adhesion Molecule-1/physiology
• Protein Binding

• R01 HL091950 NHLBI NIH HHS
• R01 HL087036 NHLBI NIH HHS
• HL091950 NHLBI NIH HHS
• UL1 TR000003 NCATS NIH HHS
• UL1TR000003 NCATS NIH HHS
• HL087036 NHLBI NIH HHS

• Biomarkers, Tumor/blood
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/pathology
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Solubility
• Vascular Endothelial Growth Factor Receptor-1/blood

Endothelial cell injury is an important component of acute lung injury. Platelet-endothelial cell adhesion molecule-1 (PECAM1) is a transmembrane protein that connects endothelial cells to one another and can be detected as a soluble, truncated protein (sPECAM1) in serum. We hypothesized that injurious mechanical ventilation (MV) leads to shedding of PECAM1 from lung endothelial cells resulting in increasing sPECAM1 levels in the systemic circulation.

We studied 36 Sprague–Dawley rats in two prospective, randomized, controlled studies (healthy and septic) using established animal models of ventilator-induced lung injury. Animals (n = 6 in each group) were randomized to spontaneous breathing or two MV strategies: low tidal volume (V_T) (6 ml/kg) and high-V_T (20 ml/kg) on 2 cmH₂O of positive end-expiratory pressure (PEEP). In low-V_T septic animals, 10 cmH₂O of PEEP was applied. We performed pulmonary histological and physiological evaluation and measured lung PECAM1 protein content and serum sPECAM1 levels after four hours ventilation period.

High-V_T MV caused severe lung injury in healthy and septic animals, and decreased lung PECAM1 protein content (P < 0.001). Animals on high-V_T had a four- to six-fold increase of mean sPECAM1 serum levels than the unventilated counterpart (35.4 ± 10.4 versus 5.6 ± 1.7 ng/ml in healthy rats; 156.8 ± 47.6 versus 35.6 ± 12.6 ng/ml in septic rats) (P < 0.0001). Low-V_T MV prevented these changes. Levels of sPECAM1 in healthy animals on high-V_T MV paralleled the sPECAM1 levels of non-ventilated septic animals.

Our findings suggest that circulating sPECAM1 may represent a promising biomarker for the detection and monitoring of ventilator-induced lung injury.

• Apoptosis
• Caspase
• Cd31
• Cd44
• Cell Proliferation
• Endothelial Cell
• Survivin
• Vascular Biology
• Western Blotting

While bone marrow (BM)-derived cells have been comprehensively studied for their propitious pre-clinical results, clinical trials have shown controversial outcomes. Unlike previously acknowledged, more recent studies have now confirmed that humoral and paracrine effects are the key mechanisms for tissue regeneration and functional recovery, instead of transdifferentiation of BM-derived cells into cardiovascular tissues. The progression of the understanding of BM-derived cells has further led to exploring efficient methods to isolate and obtain, without mobilization, sufficient number of cell populations that would eventually have a higher therapeutic potential. As such, hematopoietic CD31⁺ cells, prevalent in both bone marrow and peripheral blood, have been discovered, in recent studies, to have angiogenic and vasculogenic activities and to show strong potential for therapeutic neovascularization in ischemic tissues. This article will discuss recent advancement on BM-derived cell therapy and the implication of newly discovered CD31⁺ cells.

• Bone marrow
• CD31
• Cardiovascular repair
• Cell therapy
• Neovascularization
• Paracrine

• autism
• pecam-1
• p-selectin
• cd31
• cd62-p
• adhesion

• ve-cadherin
• β-catenin
• pecam-1
• cd31
• mcp-1
• endothelial cells
• neuroinflammation