Faculty Collaboration Database

Enhanced proliferation and migration of vascular smooth muscle cells in response to vascular injury under hyperglycemic conditions is controlled by beta3 integrin signaling. Int J Biochem Cell Biol 2010 Jun;42(6):965-74

Date

02/27/2010

Pubmed ID

20184965

Pubmed Central ID

PMC2862848

DOI

10.1016/j.biocel.2010.02.009

Scopus ID

2-s2.0-77953812743 (requires institutional sign-in at Scopus site)   48 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, beta3 integrin inhibition in diabetic patients confers protection from restenosis, little is known regarding the role of beta3 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 beta3 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 PKCbeta in an integrin beta3-dependent manner. Hyperglycemia also promoted SMC filopodia formation and cell migration, both of which required alphaVbeta3, PKCbeta, and ERK activity. Furthermore, the integrin-kinase association was regulated by the alphaVbeta3 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 beta3 integrin signaling.

Author List

Panchatcharam M, Miriyala S, Yang F, Leitges M, Chrzanowska-Wodnicka M, Quilliam LA, Anaya P, Morris AJ, Smyth SS

Author

Magdalena Chrzanowska PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Atherosclerosis
Cell Movement
Cell Proliferation
Diabetes Mellitus, Experimental
Diabetic Angiopathies
Endothelium, Vascular
Humans
Hyperglycemia
Integrin alphaVbeta3
Mice
Mice, Knockout
Myocytes, Smooth Muscle
Protein Kinase C
Protein Kinase C beta
Signal Transduction
Thrombospondins
Wound Healing