Intramural Administration of Translational Inhibitor Puromycin Upon Balloon Angioplasty Inhibits SMC Proliferation and Protein Synthesis-Vascular Proteome Profiling Analysis.

Abstract

Introduction: Percutaneous transluminal coronary angioplasty (PTCA) is an effective procedure to decrease the severity of stenotic coronary atherosclerotic lesions. However, its long-term success is limited by the formation of restenosis or neointima by increased proliferation of smooth muscle cells (SMCs) and synthesis of extracellular matrix. Polypeptide growth factors are potent SMC mitogens and are involved in SMC proliferation and extracellular matrix (ECM) synthesis. In this line, inhibition of de novo protein synthesis might be beneficial.

Methods: We examined the effects of different concentrations of translational inhibitor puromycin on SMC proliferation and apoptosis, in vitro. Further, we examined the effects of local administration of puromycin in a rabbit balloon injury model of the iliac artery.

Results: Injection of puromycin or its vehicle was performed with an infusion-balloon catheter directly into the vessel wall during angioplasty. PTA in the vehicle group resulted in neointima formation 3 weeks after the vascular intervention. In contrast, puromycin treatment resulted in a significant reduction of intima-media ratio. We observed decreased elastin and collagen III synthesis in puromycin-treated animals. With proteomics, we could demonstrate reduced protein expression of lamin, vimentin, alpha-1 antitrypsin, alpha-actin allowing puromycin treatment. In in vitro experiments, puromycin decreased SMCs proliferation (i.e., BrdU incorporation) following FCS stimulation.

Perspective: Based on the data from our animal experiments, aministration of puromycin directly into the vessel wall during angioplasty may be effective in preventing or reducing restenosis in humans.