Transforming growth factor-beta, cell signaling and cardiovascular disorders.

Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor with a wide range of potential effects on growth, differentiation, extracellular matrix accumulation and the immune system. It has been implicated in many cardiovascular disorders. TGF-beta's actions are mediated via a complex between its type I and type II receptors resulting in the phosphorylation of receptor-specific Smads followed by their passage to the nucleus where they influence many transcriptional responses. TGF-beta has important roles in the development of the neointima and constrictive remodeling associated with angioplasty. In atherosclerosis its actions are yet to be fully elucidated but its ability to control the immune system has profound effects on lesion development, particularly by influencing the types of lesions that develop. TGF-beta can also induce arteriogenesis and markedly influences angiogenic processes, possessing both pro- and anti-angiogenic effects. It is also a major contributor to the development of various cardiovascular fibrotic disorders including those in the vasculature, heart and kidney. Targeting TGF-beta prevents neointima formation and the constrictive remodeling associated with angioplasty and also prevents the development of many fibrotic disorders. This review summarizes TGF-beta signaling pathways, the mechanisms by which TGF-beta contributes to many of these cardiovascular diseases and examines the therapeutic potential of targeting TGF-beta actions in preventing these disorders.