Transforming growth factor-β regulation of proteoglycan synthesis in vascular smooth muscle: Contribution to lipid binding and accelerated atherosclerosis in diabetes

Sundy N.Y. Yang, Micah L. Burch, Lisa R. Tannock, Stephen Evanko, Narin Osman, Peter J. Little

Research output: Contribution to journalReview articlepeer-review

49 Citations (SciVal)

Abstract

Atherosclerosis is accelerated in the setting of diabetes, but the factors driving this phenomenon remain elusive. Hyperglycemia leads to elevated levels of transforming growth factor (TGF)-β and TGF-β has been implicated as a factor in atherosclerosis. Given the established association between hyperglycemia and elevated TGF-β, it is plausible that elevated TGF-β levels in diabetes play a pathogenic role in the development of accelerated atherosclerosis. TGF-β is a potent regulator of extracellular matrix synthesis, including many actions on proteoglycan synthesis that lead to increased binding to low-density lipoprotein and therefore potentially increased lipid retention in the vessel wall and accelerated atherosclerosis. TGF-β signals through the canonical TGF-β receptor I-mediated phosphorylation of Smad transcription factors and TGF-β signaling is also known to involve, positively and negatively, interactions with the mitogen-activated protein kinase pathways. The focus of the present review is on the effects of TGF-β on proteoglycan synthesis in vascular smooth muscle and particularly the signaling pathways through which TGF-β exerts its effects, because those pathways may be therapeutic targets for the prevention of pathological modifications in the proteoglycan component of the vessel wall in the vascular diseases of diabetes.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalJournal of Diabetes
Volume2
Issue number4
DOIs
StatePublished - Dec 2010

Keywords

  • Smads
  • macrovascular disease
  • response to retention

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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