TY - JOUR
T1 - 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
AU - Nelson, Jun
AU - Wu, Yi
AU - Jiang, Xiaohua
AU - Berretta, Remus
AU - Houser, Steven
AU - Choi, Eric
AU - Wang, Jingfeng
AU - Huang, Jian
AU - Yang, Xiaofeng
AU - Wang, Hong
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - Cell therapy
KW - Endothelial repair
KW - Vascular remodeling
UR - http://www.scopus.com/inward/record.url?scp=84940421901&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000356859100035&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1096/fj.14-267989
DO - 10.1096/fj.14-267989
M3 - Article
C2 - 25854700
SN - 0892-6638
VL - 29
SP - 3085
EP - 3099
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -