Dietary Antioxidants, Vascular Inflammation, and Heart Disease
Principal Investigator: Balz Frei, Ph.D.
The research program in my laboratory is aimed at understanding the role of free radicals and inflammation in human chronic disease, in particular atherosclerosis and cardiovascular disease; and the ameliorating effects of micronutrients, phytochemicals, and dietary supplements.
One of the earliest events in atherosclerosis is "activation" of the endothelium, a single cell layer lining arterial walls. Endothelial activation may be caused by increased production of free radicals and leads to increased expression of cellular adhesion molecules (CAM) and monocyte chemoattractant protein-1 (MCP-1) by these cells. As a consequence, white blood cells called monocytes are recruited to the arterial wall, where they initiate chronic inflammation and atherosclerotic lesion development. We are performing cell culture, animal, and human studies to investigate 1) the mechanisms and consequences of endothelial activation; 2) the role of transition metals like iron and copper in this process; and 3) the effectiveness of antioxidant and anti-inflammatory dietary compounds in ameliorating endothelial activation and subsequent atherosclerotic lesion development.
We have found that lipoic acid and certain metal chelators (metal-binding agents) effectively inhibit CAM and MCP-1 expression by human aortic endothelial cells and suppress vascular inflammation and atherosclerosis in experimental mice. We are currently performing two randomized clinical trials to investigate the effects of lipoic acid supplementation on oxidative stress, inflammation, serum lipids and lipoproteins, blood pressure, and other coronary risk factors in healthy subjects and heart disease patients.
Additional projects in the laboratory investigate the biological mechanisms and metabolic effects of flavonoids; the interactions of lipoic acid and ascorbic acid (vitamin C) in improving vitamin C body status and antioxidant defenses in humans; and the mechanisms of pharmacological doses of vitamin C in its potential cancer therapeutic effects.