|
1
|
Huang Y, Qian JY, Cheng H, Li XM. Effects of shear stress on differentiation of stem cells into endothelial cells. World J Stem Cells 2021; 13:894-913. [PMID: 34367483 PMCID: PMC8316872 DOI: 10.4252/wjsc.v13.i7.894] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/20/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Stem cell transplantation is an appealing potential therapy for vascular diseases and an indispensable key step in vascular tissue engineering. Substantial effort has been made to differentiate stem cells toward vascular cell phenotypes, including endothelial cells (ECs) and smooth muscle cells. The microenvironment of vascular cells not only contains biochemical factors that influence differentiation but also exerts hemodynamic forces, such as shear stress and cyclic strain. More recently, studies have shown that shear stress can influence the differentiation of stem cells toward ECs. A deep understanding of the responses and underlying mechanisms involved in this process is essential for clinical translation. This review highlights current data supporting the role of shear stress in stem cell differentiation into ECs. Potential mechanisms and signaling cascades for transducing shear stress into a biological signal are proposed. Further study of stem cell responses to shear stress will be necessary to apply stem cells for pharmacological applications and cardiovascular implants in the realm of regenerative medicine.
Collapse
Affiliation(s)
- Yan Huang
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China
| | - Jia-Yi Qian
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China
| | - Hong Cheng
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China
| | - Xiao-Ming Li
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
| |
Collapse
|
|
2
|
Xia LZ, Tao J, Chen YJ, Liang LL, Luo GF, Cai ZM, Wang Z. Factors Affecting the Re-Endothelialization of Endothelial Progenitor Cell. DNA Cell Biol 2021; 40:1009-1025. [PMID: 34061680 DOI: 10.1089/dna.2021.0082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The vascular endothelium, which plays an essential role in maintaining the normal shape and function of blood vessels, is a natural barrier between the circulating blood and the vascular wall tissue. The endothelial damage can cause vascular lesions, such as atherosclerosis and restenosis. After the vascular intima injury, the body starts the endothelial repair (re-endothelialization) to inhibit the neointimal hyperplasia. Endothelial progenitor cell is the precursor of endothelial cells and plays an important role in the vascular re-endothelialization. However, re-endothelialization is inevitably affected in vivo and in vitro by factors, which can be divided into two types, namely, promotion and inhibition, and act on different links of the vascular re-endothelialization. This article reviews these factors and related mechanisms.
Collapse
Affiliation(s)
- Lin-Zhen Xia
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, China
| | - Jun Tao
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, China
| | - Yan-Jun Chen
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, China
| | - Ling-Li Liang
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, China
| | - Gui-Fang Luo
- Department of Gynaecology, The First Affiliated Hospital of University of South China, Hengyang, China
| | - Ze-Min Cai
- Pediatrics Department, The First Affiliated Hospital of University of South China, Hengyang, China
| | - Zuo Wang
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, China
| |
Collapse
|
|
3
|
Calabriso N, Stanca E, Rochira A, Damiano F, Giannotti L, Di Chiara Stanca B, Massaro M, Scoditti E, Demitri C, Nitti P, Palermo A, Siculella L, Carluccio MA. Angiogenic Properties of Concentrated Growth Factors (CGFs): The Role of Soluble Factors and Cellular Components. Pharmaceutics 2021; 13:pharmaceutics13050635. [PMID: 33946931 PMCID: PMC8146902 DOI: 10.3390/pharmaceutics13050635] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/25/2021] [Accepted: 04/27/2021] [Indexed: 12/21/2022] Open
Abstract
Blood-derived concentrated growth factors (CGFs) represent a novel autologous biomaterial with promising applications in regenerative medicine. Angiogenesis is a key factor in tissue regeneration, but the role played by CGFs in vessel formation is not clear. The purpose of this study was to characterize the angiogenic properties of CGFs by evaluating the effects of its soluble factors and cellular components on the neovascularization in an in vitro model of angiogenesis. CGF clots were cultured for 14 days in cell culture medium; after that, CGF-conditioned medium (CGF-CM) was collected, and soluble factors and cellular components were separated and characterized. CGF-soluble factors, such as growth factors (VEGF and TGF-β1) and matrix metalloproteinases (MMP-2 and -9), were assessed by ELISA. Angiogenic properties of CGF-soluble factors were analyzed by stimulating human cultured endothelial cells with increasing concentrations (1%, 5%, 10%, or 20%) of CGF-CM, and their effect on cell migration and tubule-like formation was assessed by wound healing and Matrigel assay, respectively. The expression of endothelial angiogenic mediators was determined using qRT-PCR and ELISA assays. CGF-derived cells were characterized by immunostaining, qRT-PCR and Matrigel assay. We found that CGF-CM, consisting of essential pro-angiogenic factors, such as VEGF, TGF-β1, MMP-9, and MMP-2, promoted endothelial cell migration; tubule structure formation; and endothelial expression of multiple angiogenic mediators, including growth factors, chemokines, and metalloproteinases. Moreover, we discovered that CGF-derived cells exhibited features such as endothelial progenitor cells, since they expressed the CD34 stem cell marker and endothelial markers and participated in the neo-angiogenic process. In conclusion, our results suggest that CGFs are able to promote endothelial angiogenesis through their soluble and cellular components and that CGFs can be used as a biomaterial for therapeutic vasculogenesis in the field of tissue regeneration.
Collapse
Affiliation(s)
- Nadia Calabriso
- National Research Council (CNR), Campus Ecotekne, Institute of Clinical Physiology (IFC), University of Salento, Via per Monteroni, 73100 Lecce, Italy; (N.C.); (M.M.); (E.S.)
| | - Eleonora Stanca
- Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, Campus Ecotekne, University of Salento, Via per Monteroni, 73100 Lecce, Italy; (E.S.); (A.R.); (F.D.); (L.G.); (B.D.C.S.)
| | - Alessio Rochira
- Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, Campus Ecotekne, University of Salento, Via per Monteroni, 73100 Lecce, Italy; (E.S.); (A.R.); (F.D.); (L.G.); (B.D.C.S.)
| | - Fabrizio Damiano
- Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, Campus Ecotekne, University of Salento, Via per Monteroni, 73100 Lecce, Italy; (E.S.); (A.R.); (F.D.); (L.G.); (B.D.C.S.)
| | - Laura Giannotti
- Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, Campus Ecotekne, University of Salento, Via per Monteroni, 73100 Lecce, Italy; (E.S.); (A.R.); (F.D.); (L.G.); (B.D.C.S.)
| | - Benedetta Di Chiara Stanca
- Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, Campus Ecotekne, University of Salento, Via per Monteroni, 73100 Lecce, Italy; (E.S.); (A.R.); (F.D.); (L.G.); (B.D.C.S.)
| | - Marika Massaro
- National Research Council (CNR), Campus Ecotekne, Institute of Clinical Physiology (IFC), University of Salento, Via per Monteroni, 73100 Lecce, Italy; (N.C.); (M.M.); (E.S.)
| | - Egeria Scoditti
- National Research Council (CNR), Campus Ecotekne, Institute of Clinical Physiology (IFC), University of Salento, Via per Monteroni, 73100 Lecce, Italy; (N.C.); (M.M.); (E.S.)
| | - Christian Demitri
- Department of Engineering for Innovation, Campus Ecotekne, University of Salento, Via per Monteroni, 73100 Lecce, Italy; (C.D.); (P.N.)
| | - Paola Nitti
- Department of Engineering for Innovation, Campus Ecotekne, University of Salento, Via per Monteroni, 73100 Lecce, Italy; (C.D.); (P.N.)
| | - Andrea Palermo
- Implant Dentistry College of Medicine and Dentistry Birmingham, University of Birmingham, Birmingham B4 6BN, UK;
| | - Luisa Siculella
- Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, Campus Ecotekne, University of Salento, Via per Monteroni, 73100 Lecce, Italy; (E.S.); (A.R.); (F.D.); (L.G.); (B.D.C.S.)
- Correspondence: (L.S.); (M.A.C.)
| | - Maria Annunziata Carluccio
- National Research Council (CNR), Campus Ecotekne, Institute of Clinical Physiology (IFC), University of Salento, Via per Monteroni, 73100 Lecce, Italy; (N.C.); (M.M.); (E.S.)
- Correspondence: (L.S.); (M.A.C.)
| |
Collapse
|
|
4
|
Zhang B, Li D, Liu G, Tan W, Zhang G, Liao J. Impaired activity of circulating EPCs and endothelial function are associated with increased Syntax score in patients with coronary artery disease. Mol Med Rep 2021; 23:321. [PMID: 33760184 PMCID: PMC7974324 DOI: 10.3892/mmr.2021.11960] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 02/10/2021] [Indexed: 12/13/2022] Open
Abstract
It has previously been shown that the number of endothelial progenitor cells (EPCs) is negatively correlated with Syntax score in patients with coronary artery disease (CAD). However, the association between alterations in EPC function and Syntax score is still unknown. The present study evaluated the association between the activity of EPCs as well as endothelial function and Syntax score in patients with CAD and investigated the underlying mechanisms. A total of 60 patients with CAD were enrolled in 3 groups according to Syntax score, and 20 healthy subjects were recruited as the control group. The number and migratory, proliferative and adhesive activities of circulating EPCs were studied. The endothelial function was measured by flow-mediated dilatation (FMD) and the levels of nitric oxide (NO) in plasma or secreted by EPCs were detected. The number and activity of circulating EPCs were lower in patients with a high Syntax score, which was similar to the alteration in FMD. The level of NO in plasma or secreted by EPCs also decreased as Syntax score increased. There was a negative association between FMD or circulating EPCs and Syntax score. A similar association was observed between the levels of NO in plasma or secreted by EPCs and Syntax score. Patients with CAD who had a higher Syntax score exhibited lower EPC numbers or activity and weaker endothelial function, which may be associated with attenuated NO production. These findings provide novel surrogate parameters for evaluation of the severity and complexity of CAD.
Collapse
Affiliation(s)
- Bin Zhang
- Department of Cardiovascular Disease, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat‑Sen University, Jiangmen, Guangdong 529030, P.R. China
| | - Dong Li
- Clinical Experimental Center, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat‑Sen University, Jiangmen, Guangdong 529030, P.R. China
| | - Gexiu Liu
- Institute of Hematology, Medical College, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Wenfeng Tan
- Department of Cardiovascular Disease, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat‑Sen University, Jiangmen, Guangdong 529030, P.R. China
| | - Gaoxing Zhang
- Department of Cardiovascular Disease, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat‑Sen University, Jiangmen, Guangdong 529030, P.R. China
| | - Jinli Liao
- Division of Emergency Medicine, Department of General Internal Medicine, Department of Emergency Intensive Care Unit, The First Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China
| |
Collapse
|
|
5
|
Aliskiren Improved the Endothelial Repair Capacity of Endothelial Progenitor Cells from Patients with Hypertension via the Tie2/PI3k/Akt/eNOS Signalling Pathway. Cardiol Res Pract 2020; 2020:6534512. [PMID: 32566272 PMCID: PMC7275222 DOI: 10.1155/2020/6534512] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 04/21/2020] [Indexed: 12/29/2022] Open
Abstract
Background Studies show that aliskiren exerts favourable effects not only on endothelial progenitor cells (EPCs) but also on endothelial function. However, the mechanism of the favourable effect of aliskiren on EPCs from patients with hypertension is unclear and remains to be further studied. Methods The object of this study was to investigate and assess the in vitro function of EPCs pretreated with aliskiren. After treated with aliskiren, the human EPCs were transplanted into a nude mouse model of carotid artery injury, and the in vivo reendothelialization of injured artery was estimated by staining denuded areas with Evans blue dye via tail vein injection. Results We found that aliskiren increased the in vitro migration, proliferation, and adhesion of EPCs from patients with hypertension in a dose-dependent manner and improved the reendothelialization capability of these EPCs. Furthermore, aliskiren increased the phosphorylation of Tie2, Akt, and eNOS. After the blockade of the Tie2 signalling pathway, the favourable effects of aliskiren on the in vitro function and in vivo reendothelialization capability of EPCs were suppressed. Conclusions This study demonstrates that aliskiren can improve the in vitro function and in vivo reendothelialization capability of EPCs from patients with hypertension via the activation of the Tie2/PI3k/Akt/eNOS signalling pathway. These findings further indicate that aliskiren is an effective pharmacological treatment for cell-based repair in hypertension-related vascular injury.
Collapse
|
|
6
|
Reduced Circulating Endothelial Progenitor Cells and Downregulated GTCPH I Pathway Related to Endothelial Dysfunction in Premenopausal Women with Isolated Impaired Glucose Tolerance. Cardiol Res Pract 2020; 2020:1278465. [PMID: 32411442 PMCID: PMC7204339 DOI: 10.1155/2020/1278465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 12/31/2019] [Indexed: 01/23/2023] Open
Abstract
Background Individuals at a prediabetic stage have had an augmented cardiovascular disease (CVD) risk and CVD-related mortality compared to normal glucose tolerance (NGT) individuals, which may be attributed to the impaired vascular endothelial repair capacity. In this study, circulating endothelial progenitor cells' (EPCs) number and activity were evaluated, and the underlying mechanisms in premenopausal women with impaired glucose regulation were explored. Methods Circulating EPCs' number and activity and flow-mediated dilation (FMD) were compared in premenopausal women with NGT, isolated impaired fasting glucose (i-IFG), or isolated impaired glucose tolerance (i-IGT). Plasma nitric oxide (NO), EPCs-secreted NO, and intracellular BH4 levels were also measured. The key proteins (Tie2, Akt, eNOS, and GTPCH I) in the guanosine triphosphate cyclohydrolase/tetrahydrobiopterin (GTPCH/BH4) pathway and Tie2/Akt/eNOS signaling pathway were evaluated in these women. Results It was observed that the i-IGT premenopausal women not i-IFG premenopausal women had a significant reduction in circulating EPCs' number and activity as well as reduced FMD when compared to NGT subjects. Plasma NO levels or EPCs-secreted NO also decreased only in i-IGT women. The expression of GTCPH I as well as intracellular BH4 levels declined in i-IGT women; however, the alternations of key proteins' expression in the Tie2/Akt/eNOS signaling pathway were not observed in either i-IGT or i-IFG women. Conclusions The endothelial repair capacity was impaired in i-IGT premenopausal women but was preserved in i-IFG counterparts. The underlying mechanism may be associated with the downregulated GTCPH I pathway and reduced NO productions.
Collapse
|
|
7
|
Zeng H, Jiang Y, Tang H, Ren Z, Zeng G, Yang Z. Abnormal phosphorylation of Tie2/Akt/eNOS signaling pathway and decreased number or function of circulating endothelial progenitor cells in prehypertensive premenopausal women with diabetes mellitus. BMC Endocr Disord 2016; 16:13. [PMID: 26936372 PMCID: PMC4776390 DOI: 10.1186/s12902-016-0093-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 02/25/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUNDS The number and activity of circulating endothelial progenitor cells (EPCs) in prehypertension is preserved in premenopausal women. However, whether this favorable effect still exists in prehypertensive premenopausal women with diabetes is not clear. METHODS This study compared the number and functional activity of circulating EPCs in normotensive or prehypertensive premenopausal women without diabetes mellitus and normotensive or prehypertensive premenopausal women with diabetes mellitus, evaluated the vascular endothelial function in each groups, and investigated the possible underlying mechanism. RESULTS We found that compared with normotensive premenopausal women, the number and function of circulating EPCs, as well as endothelial function evaluated by flow-mediated dilatation (FMD) in prehypertensive premenopausal women were preserved. In parallel, the Tie2/Akt/eNOS signaling pathway and the plasma NO level or NO secretion of circulating EPCs in prehypertensive premenopausal women was also retained. However, in presence of normotension or prehypertension with diabetes mellitus, the number or function of circulating EPCs and FMD in premenopausal women decreased. Similarly, the phosphorylation of Tie2/Akt/eNOS signaling pathway and the plasma NO level or NO secretion of circulating EPCs was reduced in prehypertension premenopausal with diabetes mellitus. CONCLUSION The present findings firstly demonstrate that the unfavorable effects of diabetes mellitus on number and activity of circulating EPCs in prehypertension premenopausal women, which is at least partially related to the abnormal phosphorylation of Tie2/Akt/eNOS signaling pathway and subsequently reduced nitric oxide bioavailability. The Tie2/Akt/eNOS signaling pathway may be a potential target of vascular protection in prehypertensive premenopausal women with diabetes mellitus.
Collapse
Affiliation(s)
- Haitao Zeng
- Center for Reproductive Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Yanping Jiang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan, 421001, China
| | - Hailin Tang
- Cancer Center, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Zi Ren
- Center for Reproductive Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Gaofeng Zeng
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan, 421001, China.
| | - Zhen Yang
- Department of Hypertension & Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
| |
Collapse
|
|
8
|
Tseng CN, Karlöf E, Chang YT, Lengquist M, Rotzius P, Berggren PO, Hedin U, Eriksson EE. Contribution of endothelial injury and inflammation in early phase to vein graft failure: the causal factors impact on the development of intimal hyperplasia in murine models. PLoS One 2014; 9:e98904. [PMID: 24887332 PMCID: PMC4041877 DOI: 10.1371/journal.pone.0098904] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 05/08/2014] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVES Autologous veins are preferred conduits in by-pass surgery. However, long-term results are hampered by limited patency due to intimal hyperplasia. Although mechanisms involved in development of intimal hyperplasia have been established, the role of inflammatory processes is still unclear. Here, we studied leukocyte recruitment and intimal hyperplasia in inferior vena cava grafts transferred to abdominal aorta in mice. METHODS AND RESULTS Several microscopic techniques were used to study endothelium denudation and regeneration and leukocyte recruitment on endothelium. Scanning electron microscopy demonstrated denudation of vein graft endothelium 7 days post-transfer and complete endothelial regeneration by 28 days. Examination of vein grafts transferred to mice transgenic for green fluorescent protein under Tie2 promoter in endothelial cells showed regeneration of graft endothelium from the adjacent aorta. Intravital microscopy revealed recruitment of leukocytes in vein grafts at 7 days in wild type mice, which had tapered off by 28 days. At 28 and 63 days there was significant development of intimal hyperplasia. In contrast; no injury, leukocyte recruitment nor intimal hyperplasia occurred in arterial grafts. Leukocyte recruitment was reduced in vein grafts in mice deficient in E- and P-selectin. In parallel, intimal hyperplasia was reduced in vein grafts in mice deficient in E- and P-selectin and in wild type mice receiving P-selectin/E-selectin function-blocking antibodies. CONCLUSION The results show that early phase endothelial injury and inflammation are crucial processes in intimal hyperplasia in murine vein grafts. The data implicate endothelial selectins as targets for intervention of vein graft disease.
Collapse
Affiliation(s)
- Chi-Nan Tseng
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Eva Karlöf
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Ya-Ting Chang
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Mariette Lengquist
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Pierre Rotzius
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Per-Olof Berggren
- The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Ulf Hedin
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Einar E. Eriksson
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| |
Collapse
|
|
9
|
Yang Z, Xia WH, Zhang YY, Xu SY, Liu X, Zhang XY, Yu BB, Qiu YX, Tao J. Shear stress-induced activation of Tie2-dependent signaling pathway enhances reendothelialization capacity of early endothelial progenitor cells. J Mol Cell Cardiol 2012; 52:1155-1163. [PMID: 22326430 DOI: 10.1016/j.yjmcc.2012.01.019] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2011] [Revised: 01/09/2012] [Accepted: 01/24/2012] [Indexed: 11/19/2022]
Abstract
Although endothelial progenitor cells (EPCs) play a pivotal role in the endothelial repair following arterial injury and shear stress has a beneficial effect on EPCs, however, the molecular mechanism underlying the influence of EPCs on the endothelial integrity and the regulation of shear stress on the EPC signaling remained to be studied. Here, we investigated the effects of laminar shear stress on the tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2 (Tie2)-dependent signaling and its relation to in vivo reendothelialization capacity of human early EPCs. The human early EPCs were treated with shear stress. Shear stress in a dose-dependent manner increased angiopoietin-2 (Ang2)-induced migratory, adhesive and proliferatory activities of EPCs. Transplantation of EPCs treated by shear stress facilitated in vivo reendothelialization in nude mouse model of carotid artery injury. In parallel, the phosphorylation of Tie2 and Akt of EPCs in response to shear stress was significantly enhanced. With treatment of Tie2 knockdown or Akt inhibition, shear stress-induced phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) of EPCs was markedly suppressed. After Tie2/PI3K/Akt/eNOS signaling was blocked, the effects of shear stress on in vitro function and in vivo reendothelialization capacity of EPCs were significantly inhibited. The present findings demonstrate for the first time that Tie2/PI3k/Akt/eNOS signaling pathway is, at least in part, involved in the EPCs-mediated reendothelialization after arterial injury. The upregulation of shear stress-induced Tie2-dependent signaling contributes to enhanced in vivo reendothelialization capacity of human EPCs.
Collapse
Affiliation(s)
- Zhen Yang
- Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
| | | | | | | | | | | | | | | | | |
Collapse
|