[Physiological Function of Apolipoproteins and Atherosclerosis]

We have studied the physiological function of four apolipoproteins. First, apo A-I is a major component of HDL and plays a crucial role in reverse cholesterol transport. The lipid-poor apo A-I concentration in plasma was significantly increased in patients with coronary artery disease compared with healthy controls, which may be caused by the impairment of the reverse cholesterol transport pathway. Second, the plasma A-IV concentration was significantly elevated in uremic patients, and we revealed the mechanism of apo A-IV accumulation in plasma using a rat model. Third, apo B48 is associated with lipid absorption in the intestinal epithelium, but the lymph apo B48 output was not changed during the absorption of mid-chain triglycerides, unlike apo A-IV. Fourth, we showed for the first time that the cerebrospinal apo E level was reduced in early-onset Alzheimer's disease and increased in a late-onset group. Taken together, apolipoproteins show various functions via the regulation of lipid metabolism. We have also studied the effect of cytokines on atherosclerosis using cytokine knockout mice. TNF-α and IL-1β increased the number and size of atherosclerotic lesions, but IFN-γ attenuated the lesions. Plaque formation is influenced by not only the cholesterol level in plasma but also cytokine levels and other unknown factors. It may be of no merit to give cholesterol-lowering drugs to hypercholesterolemic patients without plaque. It is, thus, strongly expected that a biomarker which can predict the presence of plaque will be developed in the future.