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

Jun Nelson, Yi Wu, Xiaohua Jiang, Remus Berretta, Steven Houser, Eric Choi, Jingfeng Wang, Jian Huang, Xiaofeng Yang, Hong Wang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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-b synthase heterozygous mice fed a highmethionine diet for 8 weeks. Vascular injury was introduced by carotid air-dry endotheliumdenudation.CD34+/VEGFR2+ cells were examined by flow cytometry. HHcy reduced bonemarrow (BM) CD34+/VEGFR2+ cells and suppressed replenishment of postinjury CD34+/VEGFR2+ cells in peripheral blood (PB). Donor green fluorescent proteinpositive PC homing to the injured vessel was reduced in HHcy after CD34+ PCs from enhanced green fluorescent proteinmice were adoptively transferred following carotid injury. CD34+ PC transfusion partially reversed HHcysuppressed re-endothelialization and HHcy-induced neointimal formation. Furthermore, homocysteine (Hcy) inhibited proliferation, adhesion, and migration and suppressed b1-integrin expression and activity in human CD34+ endothelial colony-forming cells (ECFCs) isolated from PBs in a dose-dependent manner. A functionalactivating 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 b1-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 b1- integrin in progenitor cellmigration and adhesion.

Original languageEnglish
Pages (from-to)3085-3099
Number of pages15
JournalFASEB Journal
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

Keywords

  • Cell therapy
  • Endothelial repair
  • Vascular remodeling

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