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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 beta1-integrin in progenitor cell migration and adhesion
FASEB J (2015) 29:3085-99.
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 ( approximately 150 muM), which was induced in cystathionine-beta 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 beta1-integrin expression and activity in human CD34(+) endothelial colony-forming cells (ECFCs) isolated from PBs in a dose-dependent manner. A functional-activating beta1-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 beta1-integrin inhibition, which partially contributes to impaired re-endothelialization and vascular remodeling.
Publication Date: 2015-07-01.
PMCID: PMC4478803
Last updated on Saturday, August 22, 2020