OBJECTIVE-: Integrin-mediated cell adhesion to type I fibrillar collagen regulates gene and protein expression, whereas little is known of its effect on lipid metabolism. In the present study, we examined the effect of type I fibrillar collagen on cholesterol biosynthesis in human aortic smooth muscle cells (SMCs). METHODS AND RESULTS-: SMCs were cultured on either fibrillar or monomer collagen for 48 hours and [C]-acetate incorporation into cholesterol was evaluated. Fibrillar collagen reduced by 72.9±2.6% cholesterol biosynthesis without affecting cellular cholesterol levels. Fibrillar collagen also reduced 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) promoter activity (-72.6±7.3%), mRNA (-58.7±6.4%), protein levels (-35.5±8.5%), and enzyme activity (-37.7±2.2%). Intracellular levels of the active form of sterol regulatory element binding proteins (SREBP) 1a was decreased by 60.7±21.7% in SMCs cultured on fibrillar collagen, whereas SREBP2 was not significantly affected (+12.1±7.1%). The overexpression of the active form of SREBP1a rescued the downregulation of fibrillar collagen on HMG-CoA reductase levels. Blocking antibody to α2 integrin partially reversed the downregulation of HMG-CoA reductase mRNA expression. Finally, fibrillar collagen led to an intracellular accumulation of unprenylated Ras. CONCLUSIONS-: Our study demonstrated that α2β1 integrin interaction with fibrillar collagen affected the expression of HMG-CoA reductase, which led to the inhibition of cholesterol biosynthesis in human SMCs.
|Number of pages||7|
|Journal||Arteriosclerosis, Thrombosis, and Vascular Biology|
|Publication status||Published - Oct 2009|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine