Enhanced proliferation and migration of vascular smooth muscle cells in response to vascular injury under hyperglycemic conditions is controlled by β3 integrin signaling

Manikandan Panchatcharam, Sumitra Miriyala, Fanmuyi Yang, Michael Leitges, Magdalena Chrzanowska-Wodnicka, Lawrence A. Quilliam, Paul Anaya, Andrew J. Morris, Susan S. Smyth

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Atheroma formation and restenosis following percutaneous vascular intervention involve the growth and migration of vascular smooth muscle cells (SMCs) into neointimal lesions, in part due to changes in the extracellular matrix. While some clinical studies have suggested that, in comparison to non-diabetics, β3 integrin inhibition in diabetic patients confers protection from restenosis, little is known regarding the role of β3 integrin inhibition on SMC responses in this context. To understand the molecular mechanisms underlying integrin-mediated regulation of SMC function in diabetes, we examined SMC responses in diabetic mice deficient in integrin β3 and observed that the integrin was required for enhanced proliferation, migration and extracellular regulated kinase (ERK) activation. Hyperglycemia-enhanced membrane recruitment and catalytic activity of PKCβ in an integrin β3-dependent manner. Hyperglycemia also promoted SMC filopodia formation and cell migration, both of which required αVβ3, PKCβ, and ERK activity. Furthermore, the integrin-kinase association was regulated by the αVβ3 integrin ligand thrombospondin and the integrin modulator Rap1 under conditions of hyperglycemia. These results suggest that there are differences in SMC responses to vascular injury depending on the presence or absence of hyperglycemia and that SMC response under hyperglycemic conditions is largely mediated through β3 integrin signaling.

Original languageEnglish (US)
Pages (from-to)965-974
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume42
Issue number6
DOIs
StatePublished - Jun 1 2010

Keywords

  • Hyperglycemia
  • Intima
  • Proliferation
  • Restenosis
  • Smooth muscle cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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