HeartResearchSeries.org

Date: February 6, 2008, 4:00 - 5:00 pm
Location: Gerstenzang 121, Brandeis University, Waltham, MA
"Discrete roles of apoA-I and apoE in the biogenesis of HDL species: Lessons learned from adenovirus-mediated gene transfer in apoA-I-deficient mice." [view recording of presentation>>]
Dr. Vassilis Zannis, Ph.D. , Professor of Biochemistry, Departments of Medicine and Biochemistry, Boston University School of Medicine, Boston, MA

Abstract:
Using adenovirus-mediated gene transfer in apoA-I-deficient mice, we have established that apoA-I mutations inhibit discrete steps in a pathway that leads to the biogenesis and remodeling of HDL. To this point, five discrete categories of apoA-I mutants have been characterized that may affect the interactions of apoA-I with ABCA1 or LCAT or may influence the plasma PLTP activity or may cause various forms of dyslipidemia.Biogenesis of HDL is not a unique property of apoA-I. Using adenovirus-mediated gene transfer of apoE in apoA-I- or ABCA1-deficient mice, we have established that apoE also participates in a novel pathway of biogenesis of apoE-containing HDL particles. This process requires the functions of the ABCA1 lipid transporter and LCAT and it is promoted by substitution of hydrophobic residues in the 261 to 269 region of apoE by Ala.The apoE-containing HDL particles formed in the circulation may have atheroprotective properties. ApoE-containing HDL may also have important biological functions in the brain that confer protection from Alzheimer’s disease.

Date: October 3, 2007, 4:00 - 5:00 pm
Location: Gerstenzang 121, Brandeis University, Waltham, MA
"Diet and Heart Disease: The Seven Countries and Beyond" [view presentation slides>>]
Dr. Walter C. Willett, M.D., Dr. P.H., Harvard University Medical School, Boston, MA

Abstract:
Studies of different populations worldwide and of migrants from low- to high-risk regions indicate that coronary heart disease (CHD) is potentially almost entirely preventable. Mechanistic studies during the last decade have indicated that many biological pathways can lead to CHD, and the opportunities for prevention have thus been expanded.

Smoking accounts for about one third of myocardial infarctions in Western countries, and overweight and obesity contribute similarly. Reducing intake of total fat as a percent of calories is not an effective means for prevention, but multiple lines of evidence indicate that the type of dietary fat has a major impact on risk of CHD. Intake of trans fat from partially hydrogenated vegetable oils most strongly increases the risk, saturated fat is weakly associated with greater risk, monounsaturated fats moderately decrease risk, and polyunsaturated fats strongly decrease risk. Both N-6 and N-3 polyunsaturated fatty acids contribute to lower risk. The form of dietary carbohydrate also appears to influence risk of CHD importantly; highly refined starches are related to increased risk, but consumption of whole-grain, high-fiber cereal products have consistently been associated with lower risks. Higher consumption of fruits and vegetables contributes to lower risk, probably by multiple mechanisms. Many issues remain to be settled, including the optimal mix of mono- and polyunsaturated fatty acids, the optimal amounts of N-3 and N-6 fatty acids, the amount and source of protein, and the effects of antioxidants, other phytochemicals and minerals. From our long-term studies, we have calculated that modest dietary changes, together with avoidance of smoking, regular physical activity, and maintenance of a healthy body weight can reduce rates of coronary heart disease by over 80%. Failure to take advantage of dietary and lifestyle means of preventing these diseases represents a tremendous lost opportunity for improved health and wellbeing.