The Albany SCOR for atherosclerosis is designed to combine the work of basic scientists with that of clinical scientists. In the current phase the major part of the work is directed by the basic scientists. As new ideas for treatment and prevention emerge the balance will swing toward the clinical scientists. Our overall goal is to attack atherosclerosis at any point where it can help people. Possible points include: 1) prevention of development of initial phase of atherosclerosis; 2) slowing of progression of atherosclerotic process so that complications do not develop; 3) arresting progression after it has already started; 4) causing regression of lesions already developed; 5) leaving the atherosclerotic process uncontrolled but preventing reducing complications such as myocardial infarction and sudden death. Our work is directed toward all fivepoints but mainly involves 1,2 & 3. Underlying theoretical basis for the work includes three premises all of which we consider to be proved beyond reasonable doubt: 1) excessive cholesterol in the arterial wall is the principal accelerating factor in the development of clinically significant atherosclerotic lesions; 2) hyperplasia of mesenchymal cells (smooth muscle cells and their derivatives) and their biosynthetic and degradation products is one of the most prominent part of atherosclerotic lesion especially in early stages; 3) necrosis of cells is present from the beginning and becomes one of the most important parts in late stages when extensive regions of lipid-rich debris are present (atheroma formation). Thus studies are directed toward factors involved in whole body cholesterol balance, permeability of arterial wall to cholesterol and associated substances, biochemical and physical elements controlling cellular proliferation and effect on cellular integrity of metabolic changes and possible toxic substances including cholesterol and its oxidation derivatives. In addition, we are investigating possible toxic effects of potential therapeutic agents on the artery and on other tissues.