TGF-beta and Atherosclerosis in Man

The transforming growth factor type-beta (TGF-beta) superfamily of ligands, receptors, binding proteins and ligand traps together plays a key role in the maintenance of normal blood vessel wall structure. Specific defects in genes encoding superfamily members have now been linked to a range of cardiovascular syndromes involving loss of healthy vessel architecture, including hypertension and aneurysm. However the contribution of TGF-beta to the development of atherosclerosis is simultaneously more subtle and more complex. TGF-beta ligands are produced by a range of different cell types, which also regulate release of the active cytokine that, in turn, signals through multiple receptor complexes on different cell types. Recent evidence suggests that the T cell may be both a key source of TGF-beta1 and a key target for its effects during atherogenesis, as in other chronic inflammatory disorders. Here we review the evidence for the role of TGF-beta in the human vasculature during atherogenesis, and evaluate the available data in the context of our knowledge from animal models of the disease.