Molecular atherectomy for restenosis

Abstract

Receptors for basic (b) and acidic (a) fibroblast growth factor (FGF) are upregulated in activated smooth muscle cells. These cells, which proliferate in response to bFGF, can thus be killed by a conjugate of bFGF and the ribosome-inactivating enzyme, saporin (which, by itself, does not enter the cells). Quiescent smooth muscle cells and other cells that have few FGF receptors are not killed. In vivo, bFGF-saporin transiently inhibits smooth muscle cell proliferation and neointimal accumulation after balloon injury to the rat carotid artery. Delivery of saporin, diagnostic imaging agents, or antisense oligodeoxynucleotides might be made even more selective by linking these substances to antibodies against the extracellular domains of the putative FGF receptor isoform specific for activated smooth muscle cells.

Short-term Rapamycin for Inhibition of Neointima Formation After Balloon-Mediated Aortic Injury in Rats:Is There a Window of Opportunity for Systemic Prophylaxis of Restenosis?

“…Pathological, clinical, and experimental studies have shown that angioplasty and/or stent placement triggers multiple cellular and molecular mechanisms that initiate a cascade of events leading to restenosis from increased VSMC proliferation, synthesis of extracellular matrix, and arterial narrowing. [21][22][23] Previous studies of systemic therapy to prevent recurrent stenosis have been largely disappointing. [8][9][10][11][12] Besides the assumption that former pharmacological concepts focused on the wrong drugs and/or targets, these studies may have been negative because adequate drug levels were not achieved at the angioplasty site.…”