Inhibitory mechanisms by which suramin may attenuate neointimal formation after balloon angioplasty

Restenotic neointimal lesions, a major limitation to coronary angioplasty, develop in response to diverse signals and depend on three properties of ac tivated arterial smooth muscle cells (SMCs): proliferation, migration, and abnormal production of extracellular matrix. Most of the pharmacologic appr oaches targeting specific pathogenic factors facilitating development of re stenosis have failed in clinical trials. Our results indicate that the poly sulfonated naphthylurea suramin, a "non-specific drug" that interferes with multiple cellular proteins, inhibits neointimal formation in rabbit iliac arteries after balloon-catheter injury administered throughout the critical period of several weeks after the procedure. In vitro studies aimed at dis secting the mechanism(s) underlying the suramin-dependent effect demonstrat ed that, in addition to an inhibitory effect on SMC proliferation, suramin inhibited fibronectin and elastin deposition and the migration of SMCs thro ugh elastin membranes and into scratch gaps of monolayer cultures. We also demonstrated that suramin causes cell-surface accumulation of the elastin b inding protein, a receptor that not only anchors SMCs to the extracellular matrix, but also inhibits SMC response to interleukin-1 beta (IL-1 beta). W e conclude that suramin acts as a multitarget inhibitor of SMC activation a nd has a therapeutic potential as an agent that may attenuate arterial rest enosis after angioplasty.