Fibrillar collagen inhibits cholesterol biosynthesis in human aortic smooth muscle cells

Nicola Ferri, Elisa Roncalli, Lorenzo Arnaboldi, Simone Fenu, Olena Andrukhova, Seyedhossein Aharinejad, Marina Camera, Elena Tremoli, Alberto Corsini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1631-1637
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number10
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Cholesterol
  • HMG-CoA
  • Integrins
  • Mevalonate
  • Ras

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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