In studies with mice published in the Dec. 1, 2004 issue of the Journal of Clinical Investigation, the researchers found that drugs that activate two types of proteins called peroxisome proliferators-activated receptors (PPARs), specifically PPAR-gamma and PPAR-alpha, have a direct effect in the artery wall that prevents the accumulation of cholesterol in atherosclerotic lesions by up to 70 percent, as compared to untreated mice fed a high cholesterol diet. The scientists also determined the molecular pathways taken by the two versions of the PPAR drugs, a finding that could potentially be used to develop new anti-atherosclerotic medications.
"While current preventative therapy for cardiovascular disease is primarily based on reducing global risk factors such as hypertension, cholesterol levels and smoking, these findings provide a potential new strategy for the prevention and treatment of atherosclerosis," said the study's co-senior author, Christopher Glass, M.D., Ph.D., UCSD professor of Cellular and Molecular Medicine. "We've shown that drugs that activate PPAR-gamma and PPAR-alpha will not only reduce triglyceride levels and improve insulin levels, as previously known, but will also inhibit key processes in the artery wall that are directly responsible for the development of atherosclerosis."
Nearly 5 million Americans have atherosclerosis, which is the deposit of fatty substances, cholesterol and waste materials on the innermost layer of the walls of large and medium-sized arteries. These plaques, as they are called, can grow significantly large enough to restrict blood flow and cause a heart attack.