Coronary Repair and Restenosis Cellular Basis for Antisense Approaches

Coronary repair and restenosis are complex processes that likely differ from the established paradigm, which has been based on numerous observations with cultured smooth muscle cells and the response of non-coronary vascular beds to injury. Pluripotent mesenchymal ceils are present in the adventitia and may migrate into the region of underlying coronary lesions during the process of atherogenesis. The activation of these cells appears to play an important role in the development of restenosis. This includes fibroblast proliferation, their differentiation to myofibroblasts, and the synthesis of extracellular matrix proteins. Antisense oligomers against several cell cycle regulating genes inhibit cell proliferation and neointimal formation in various animal models. These compounds are pleiotropic, thus exerting their biological effects through several mechanisms. It remains to be determined whether the prevention of cell proliferation with antisense oligomers is sufficient to inhibit other important manifestations of vascular cell activation (eg, remodeling and lipid retention), which play roles in the development of coronary restenosis.