Inhibition Of Vascular Smooth Muscle Cell Proliferation By Hammerhead Ribozyme That Specifically Cleaves C-myc MRNA

Percutaneous transluminal coronary angioplasty (PTCA) is the most effective nonoperative method to treat coronary heart disease. However, thirty five to fifty percent of patients who have undergone a single-vessel angioplasty develop clinically significant restenosis within six months of the procedure. Histopathological studies have shown that restenosis after angioplasty is characterized by migration of medial smooth muscle cells to the intima, followed by hyperproliferation and excessive matrix deposition by these neointimal cells. Although the underlying mechanisms driving the restenotic process are still a matter of debate, it is widely believed that preventing the injury-induced activation and proliferation of media smooth muscle cells after angioplasty could prevent intimal thicking and restenosis.The c-myc oncogene is an immediate early response gene and has long been implicated in the control of normal and abnormal cell proliferation, c-myc encodes a sequence-specific DNA-binding nuclear phosphoprotein thought to be involved in transcriptional modulation. After angioplasty, mitogen stimulation of quiescent vascular smooth muscle cells rapidly induces c-myc with an overexpression. Subsequently, c-myc expression in vascular smooth muscle cells maintained at a constant low level throughout the first and subsequent cell cycles. C-my thus appears to have a role both...