This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Qureshi, I. Articles by Moursi, M. M Search for Related Content PubMed PubMed Citation Articles by Qureshi, I. Articles by Moursi, M. M Social Bookmarking                   What's this?

Homocysteine-induced vascular dysregulation is mediated by the NMDA receptor

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA, Department of Surgery, Division of Vascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Hongjiang Chen

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA, Department of Surgery, Division of Vascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Aliza T Brown

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA, Department of Surgery, Division of Vascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Ryan Fitzgerald

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA, Department of Surgery, Division of Vascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Xingjian Zhang

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA, Department of Surgery, Division of Vascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Julie Breckenridge

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA

Rafi Kazi

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA

Amy J Crocker

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA

Markus C Stühlingexsr

Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA

Kenneth Lin

Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA

John P Cooke

Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA

John F Eidt

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA, Department of Surgery, Division of Vascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Mohammed M Moursi

Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA, Department of Surgery, Division of Vascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA, mmmoursi{at}uams.edu

Elevated plasma homocysteine accelerates myointimal hyperplasia and luminal narrowing after carotid endarterectomy. N-methyl D aspartate receptors (NMDAr) in rat cerebrovascular cells are involved in homocysteine uptake and receptor-mediated stimulation. In the vasculature, NMDAr subunits (NR1, 2A-2D) have been identified by sequence homology in rat aortic endothelial cells. Exposure of these cells to homocysteine increased expression of receptor subunits, an effect that was attenuated by dizocilpine (MK801), a noncompetitive NMDA inhibitor. The objective of this study was to investigate the existence of an NMDAr in rat vascular smooth muscle (A7r5) cells, and also the effect of homocysteine on vascular dysregulation as mediated by this receptor. Subunits of the NMDAr (NR1, 2A-2D) were detected in the A7r5 cells by using the reverse transcriptase polymerase chain reaction and Western blotting. Homocysteine induced an increase in A7r5 cell proliferation, which was blocked by MK801. Homocysteine, in a dose and time dependent manner, increased expression of matrix metallinoproteinase-9 and interleukin-1beta, which have been implicated in vascular smooth muscle cell migration and/or proliferation. Homocysteine reduced the vascular elaboration of nitric oxide and increased the elaboration of the nitric oxide synthase inhibitor, asymmetric dimethylarginine. All of these homocysteine mediated effects were inhibited by MK801. NMDAr exist in vascular smooth muscle cells and appear to mediate, at least in part, homocysteine-induced dysregulation of vascular smooth muscle cell functions.

Key Words: cells • homocysteine • nitric oxide • peripheral vascular disease • smooth muscle

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?