Hyperhomocysteinemia suppresses bone marrow CD34+/VEGF receptor 2+ cells and inhibits progenitor cell mobilization and homing to injured vasculature-a role of β1-integrin in progenitor cell migration and adhesion
| Autor: | Jun, Nelson, Yi, Wu, Xiaohua, Jiang, Remus, Berretta, Steven, Houser, Eric, Choi, Jingfeng, Wang, Jian, Huang, Xiaofeng, Yang, Hong, Wang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Integrin beta1 Green Fluorescent Proteins Hematopoietic Stem Cell Transplantation Hyperhomocysteinemia Cystathionine beta-Synthase Antigens CD34 Bone Marrow Cells Mice Transgenic Vascular Remodeling Hematopoietic Stem Cells Vascular Endothelial Growth Factor Receptor-2 Colony-Forming Units Assay Mice Inbred C57BL Disease Models Animal Mice Research Communication Cell Movement Neointima cardiovascular system Cell Adhesion Animals Humans Carotid Artery Injuries |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 29(7) |
| ISSN: | 1530-6860 |
| Popis: | Hyperhomocysteinemia (HHcy) impairs re-endothelialization and accelerates vascular remodeling. The role of CD34+/VEGF receptor (VEGFR) 2+ progenitor cells (PCs) in vascular repair in HHcy is unknown. We studied the effect of HHcy on PCs and its role in vascular repair in severe HHcy (∼150 μM), which was induced in cystathionine-β synthase heterozygous mice fed a high-methionine diet for 8 weeks. Vascular injury was introduced by carotid air-dry endothelium denudation. CD34+/VEGFR2+ cells were examined by flow cytometry. HHcy reduced bone marrow (BM) CD34+/VEGFR2+ cells and suppressed replenishment of postinjury CD34+/VEGFR2+ cells in peripheral blood (PB). Donor green fluorescent protein-positive PC homing to the injured vessel was reduced in HHcy after CD34+ PCs from enhanced green fluorescent protein mice were adoptively transferred following carotid injury. CD34+ PC transfusion partially reversed HHcy-suppressed re-endothelialization and HHcy-induced neointimal formation. Furthermore, homocysteine (Hcy) inhibited proliferation, adhesion, and migration and suppressed β1-integrin expression and activity in human CD34+ endothelial colony-forming cells (ECFCs) isolated from PBs in a dose-dependent manner. A functional-activating β1-integrin antibody rescued Hcy-suppressed adhesion and migration in CD34+ ECFCs. In conclusion, HHcy reduces BM CD34+/VEGFR2+ generation and suppresses CD34+/VEGFR2+ cell mobilization and homing to the injured vessel via β1-integrin inhibition, which partially contributes to impaired re-endothelialization and vascular remodeling.—Nelson, J., Wu, Y., Jiang, X., Berretta, R., Houser, S., Choi, E., Wang, J., Huang, J., Yang, X., Wang, H. Hyperhomocysteinemia suppresses bone marrow CD34+/VEGF receptor 2+ cells and inhibits progenitor cell mobilization and homing to injured vasculature—a role of β1-integrin in progenitor cell migration and adhesion. |
| Databáze: | OpenAIRE |
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