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.
© 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.