PMID- 25854700 OWN - NLM STAT- MEDLINE DCOM- 20150914 LR - 20220321 IS - 1530-6860 (Electronic) IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 29 IP - 7 DP - 2015 Jul TI - 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. PG - 3085-99 LID - 10.1096/fj.14-267989 [doi] 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 ( 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. CI - (c) FASEB. FAU - Nelson, Jun AU - Nelson J AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Wu, Yi AU - Wu Y AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Jiang, Xiaohua AU - Jiang X AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Berretta, Remus AU - Berretta R AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Houser, Steven AU - Houser S AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Choi, Eric AU - Choi E AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Wang, Jingfeng AU - Wang J AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Huang, Jian AU - Huang J AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Yang, Xiaofeng AU - Yang X AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Wang, Hong AU - Wang H AD - *Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Cardiovascular Research Center, Department of Physiology, and Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; Department of Cardiology, Sun Yixian Memorial Hospital, Zhongshan University School of Medicine, Guangzhou, China; and **Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA hongw@temple.edu. LA - eng GR - HL82774/HL/NHLBI NIH HHS/United States GR - R01 HL108910/HL/NHLBI NIH HHS/United States GR - R01 HL077288/HL/NHLBI NIH HHS/United States GR - HL108910/HL/NHLBI NIH HHS/United States GR - HL77288/HL/NHLBI NIH HHS/United States GR - HL117654/HL/NHLBI NIH HHS/United States GR - R01 HL117654/HL/NHLBI NIH HHS/United States GR - HL67033/HL/NHLBI NIH HHS/United States GR - R01 HL082774/HL/NHLBI NIH HHS/United States GR - R01 HL110764/HL/NHLBI NIH HHS/United States GR - HL110764/HL/NHLBI NIH HHS/United States GR - HL116917/HL/NHLBI NIH HHS/United States GR - HL9445/HL/NHLBI NIH HHS/United States GR - F32 HL009445/HL/NHLBI NIH HHS/United States GR - R01 HL067033/HL/NHLBI NIH HHS/United States GR - R01 HL116917/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150408 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Antigens, CD34) RN - 0 (Integrin beta1) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.7.10.1 (KDR protein, human) RN - EC 2.7.10.1 (Kdr protein, mouse) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) RN - EC 4.2.1.22 (Cystathionine beta-Synthase) SB - IM MH - Animals MH - Antigens, CD34/metabolism MH - Bone Marrow Cells/*pathology/*physiology MH - Carotid Artery Injuries/pathology/physiopathology MH - Cell Adhesion MH - Cell Movement MH - Colony-Forming Units Assay MH - Cystathionine beta-Synthase/deficiency/genetics/metabolism MH - Disease Models, Animal MH - Green Fluorescent Proteins/genetics MH - Hematopoietic Stem Cell Transplantation MH - Hematopoietic Stem Cells/pathology/physiology MH - Humans MH - Hyperhomocysteinemia/genetics/*pathology/*physiopathology MH - Integrin beta1/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Neointima/pathology/physiopathology/prevention & control MH - Vascular Endothelial Growth Factor Receptor-2/*metabolism MH - Vascular Remodeling PMC - PMC4478803 OTO - NOTNLM OT - cell therapy OT - endothelial repair OT - vascular remodeling EDAT- 2015/04/10 06:00 MHDA- 2015/09/15 06:00 PMCR- 2016/07/01 CRDT- 2015/04/10 06:00 PHST- 2014/12/09 00:00 [received] PHST- 2015/03/16 00:00 [accepted] PHST- 2015/04/10 06:00 [entrez] PHST- 2015/04/10 06:00 [pubmed] PHST- 2015/09/15 06:00 [medline] PHST- 2016/07/01 00:00 [pmc-release] AID - fj.14-267989 [pii] AID - FJ_267989 [pii] AID - 10.1096/fj.14-267989 [doi] PST - ppublish SO - FASEB J. 2015 Jul;29(7):3085-99. doi: 10.1096/fj.14-267989. Epub 2015 Apr 8.