Assistant Research Scientist, Surgical Service, SFVAMC
Assistant Professor of Surgery, UCSF

Email: robert.raffai@ucsf.edu

Peripheral arterial disease (PAD) is caused by fatty blockages, called atherosclerosis, in arteries throughout the body, including in the arms, neck, and legs. PAD normally occurs in the elderly, causing leg pains that limit walking. Advanced PAD often requires amputation of feet, and operations to prevent death from kidney failure, heart failure, and stroke. Diabetes is a major risk factor for PAD, causing atherosclerosis to develop early in life in peripheral arteries very close to limbs. How and why this occurs, and whether high blood sugar (hyperglycemia) is responsible, is not known. The lack of genetically engineered mouse models of PAD has severely blocked research aimed at understanding how diabetes accelerates PAD. Dr. Raffai recently developed a mouse model of PAD. In these mice, PAD develops naturally because of high blood lipids. However, a genetic switch allows Dr. Raffai to lower their blood lipids and reverse atherosclerosis. This unique PAD mouse will be used to test if and how hyperglycemia can cause premature PAD. Genetic analysis will be used to study how hyperglycemia causes atherosclerosis to develop in arteries close to limbs and organs. Lastly, research will be done to test if hyperglycemia can block the reversal of atherosclerosis, and if insulin treatment can overcome this block. Results from these studies will provide valuable new knowledge to help fight PAD, a devastating and tragic disorder frequently affecting our growing population of veterans who suffer from diabetes.

Raffai RL, Loeb SM, Weisgraber KH. 2005. Apolipoprotein E promotes the regression of atherosclerosis independently of lowering plasma cholesterol levels. Arterioscler Thromb Vasc Biol 25(2):436-41.