Gene therapy approaches for the prevention of restenosis.

Abstract

Experimental gene-therapeutic approaches for the prevention of restenosis after balloon angioplasty are the major source of our insight into pathways operative in the process of vascular renarrowing. We now understand that thrombosis and inflammation are the key mechanisms triggering vascular "healing" in response to injury and know a multitude of potential gene-therapeutic strategies to interfere with appositional thrombus formation, proliferation and migration of vascular smooth muscle cells, lesional recruitment of inflammatory cells or excess deposition of extracellular matrix. Thus far, the major limitation for clinical anti-restenotic gene therapy are concerns about the safety and efficacy of vector systems in use for the local overexpression of transgenes, which in turn is one of the most attractive advantages of gene therapy compared to systemic drug therapy. Here, we review the molecular mechanisms operative in postangioplasty restenosis by highlighting their respective gene therapeutic approaches and the current viral and non-viral vector systems.