Regulation of alpha7-integrin expression in vascular smooth muscle by injury-induced atherosclerosis.
Injury of vascular smooth muscle cells (VSMCs) by allylamine (AAM) leads to phenotypic changes associated with atherogenic progression including increased proliferation, migration, and alterations in cell adhesion. In the present study, the relationship between AAM-induced vascular injury and expression of the alpha(7)-integrin subunit was investigated. The alpha(7)-mRNA and protein expression were examined using real-time RT-PCR, fluorescence-activated cell sorting analysis (FACS), immunohistochemistry, and immunoblotting. In cultured VSMCs from aortas of AAM-treated rats (70 mg/kg for 20 days), alpha(7)-mRNA levels were increased more than twofold compared with control cells. No change was seen in beta(1)-integrin expression. FACS analysis revealed increased cell surface expression of alpha(7)-protein (25 +/- 9%; *P < 0.05). AAM treatment of naive VSMCs enhanced alpha(7)-mRNA expression (2.4 +/- 0.7-fold, mean +/- SE; *P < 0.05). The increased alpha(7)-mRNA expression was attenuated by the amine oxidase inhibitor semicarbazide and the antioxidant pyrrolidine dithiocarbamate, which confirms a role for oxidative stress in modulating alpha(7)-expression. In vivo alpha(7)-mRNA and protein expression were enhanced in the aortas of AAM-treated rats. In addition, increased alpha(7)-integrin expression facilitated AAM VSMC adhesion to laminin more efficiently compared with control (51 +/- 2%; *P < 0.05). Chemical injury induced by AAM significantly enhances alpha(7)-integrin expression in VSMCs. These findings implicate for the first time the expression of alpha(7)-integrin during the response of VSMCs to vascular injury.
Chao
Jun-Tzu
JT
Division of Vascular Biology, Cardiovascular Research Institute, Texas A&M Uniersity System Health Science Center, 336 Joe Reynolds Medical Bldg., College Station, TX 77843, USA.
Meininger
Gerald A
GA
Patterson
Jan L
JL
Jones
Sarah A L
SA
Partridge
Charles R
CR
Neiger
Jessemy D
JD
Williams
E Spencer
ES
Kaufman
Stephen J
SJ
Ramos
Kenneth S
KS
Wilson
Emily
E
D000499:Allylamine / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D039001:Integrin alpha Chains / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; C085725:integrin alpha7; D000499:Allylamine