title: Mechanical Stress Regulates Endothelial Progenitor Cell Angiogenesis Through VEGF Receptor Endocytosis.
abstract: The clinical goal of cell-based treatment for chronic heart failure is to coordinately reconstitute the cardiomyocytes and associated circulation environment including coronary resistance arteries, arterioles, and capillary profiles.(1)) This goal can be possibly achieved by implementing multipotent adult stem cells. However, it remains a challenge to modify the capillary network in the decompensated heart. A mechanical stress model was used in this study to mimic the hemodynamic and hormonal states of the decompensated heart in vitro. The angiogenesis role of endothelial progenitor cells (EPCs) under stress has been well-recognized in vascular repair. We investigated the molecular mechanisms of EPCs in this model. We found that expression of vascular endothelial growth factor (VEGF) in EPCs was significantly decreased by mechanical stress, and this effect was accompanied by a decrease in angiogenesis in vitro. Interestingly, the defective angiogenesis can be reversed by upregulating the membrane VEGF receptor (VEGFR) endocytosis. An atypical protein kinase C (aPKC) inhibitor can promote the VEGFR internalization in EPCs and enhance the formation of vascular networks. Thus, the upregulation of VEGFR endocytosis in EPCs could be a potential therapy for the cell-based treatment of chronic heart failure by enhancing the cardiomyocytes.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Bai
authors.forename: Xingxu
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Kun
authors.initials: K
authors.lastname: Jiang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Ding
authors.forename: Donato
authors.initials: D
authors.lastname: Cappetta
authors.forename: Jingmin
authors.initials: J
authors.lastname: Zhou
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
mesh_terms: D001696:Biomechanical Phenomena / Q000502:physiology*; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000502:physiology / Q000637:transplantation; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008955:Models, Cardiovascular; D018919:Neovascularization, Physiologic / Q000502:physiology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D013312:Stress, Physiological; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor