Up-Regulated Expression of Matrix Metalloproteinases in Endothelial Cells Mediates Platelet Microvesicle-Induced Angiogenesis
| Autor: | Cheng Sun, Zhengwang Cao, Zhou Zhou, Xian-Jie Xu, Jun-Jie Bei, Shi-Bin Feng, Qiang Chen, Hou-Yuan Hu, Zhengping Yu, Wei-Bo Zhao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Blood Platelets Physiology Angiogenesis Matrix metalloproteinase inhibitor Human umbilical vein endothelial cell Neovascularization Physiologic Angiogenesis Inhibitors 030204 cardiovascular system & hematology Matrix metalloproteinase Matrix Metalloproteinase Inhibitors lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine Vasculogenesis Cell Movement Human Umbilical Vein Endothelial Cells Humans Platelet lcsh:QD415-436 Cell Proliferation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 lcsh:QP1-981 Chemistry Microvesicle Dipeptides Microvesicles Cell biology Up-Regulation 030104 developmental biology Matrix Metalloproteinase 9 Platelet microvesicle Matrix Metalloproteinase 2 |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 41, Iss 6, Pp 2319-2332 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Platelet microvesicles (PMVs) contribute to angiogenesis and vasculogenesis, but the mechanisms underlying these contributions have not been fully elucidated. In the present study, we investigated whether PMVs regulate the angiogenic properties of endothelial cells (ECs) via mechanisms extending beyond the transport of angiogenic regulators from platelets. Methods: In vitro Matrigel tube formation assay and in vivo Matrigel plug assay were used to evaluate the pro-angiogenic activity of PMVs. The effects of PMVs on the migration of human umbilical vein endothelial cells (HUVECs) were detected by transwell assay and wound-healing assay. Real-time PCR and western blot were conducted to examine mRNA and protein expression of pro-angiogenic factors in HUVECs. Matrix metalloproteinase (MMP) activity was assayed by gelatin zymography. Moreover, the effects of specific MMP inhibitors were tested. Results: PMVs promoted HUVEC capillary-like network formation in a dose-dependent manner. Meanwhile, PMVs dose-dependently facilitated HUVEC migration. Levels of MMP-2 and MMP-9 expression and activity were up-regulated in HUVECs stimulated with PMVs. Inhibition of MMPs decreased their pro-angiogenic and pro-migratory effects on HUVECs. Moreover, we confirmed the pro-angiogenic activity of PMVs in vivo in mice with subcutaneous implantation of Matrigel, and demonstrated that blockade of MMPs attenuated PMV-induced angiogenesis. Conclusion: The findings of our study indicate that PMVs promote angiogenesis by up-regulating MMP expression in ECs via mechanism extending beyond the direct delivery of angiogenic factors. |
| Databáze: | OpenAIRE |
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