Growth factors and vascular smooth muscle cell growth responses.

The accumulation of vascular smooth muscle cells plays an important role in the development of atherosclerotic plaques, and in the restenotic process occurring after balloon angioplasty. Accumulation results from the synergistic effects of various growth factors and cytokines, acting to induce both proliferation and migration. Additionally, a variety of matrix proteins and extracellular proteases modulate the growth responses and phenotype of vascular smooth muscle cells. One of the important effects of growth factors such as platelet-derived growth factors, fibroblast growth factor, angiotensin II, and thrombin is to up-regulate insulin-like growth factor (IGF)-1 receptors on vascular smooth muscle cells. Furthermore, agonists that bind to G-protein-coupled receptors, such as angiotensin II and thrombin, interact with the IGF-1 receptor signalling pathway. Thus, growth factor-stimulated up-regulation of IGF-1 receptors is critical in mediating the proliferative responses to multiple growth factors.