Atheroma formation: defective control in the intimal round-trip of cholesterol.

This article is based on the concluding remarks by the author at the Ninth Paavo Nurmi Symposium on 'Lipoproteins and the Pathobiology of the Arterial Intima'. . . . Circulating cholesterol is carried into the arterial intima, the site of atherogenesis, in low-density lipoprotein (LDL) particles, and from the intima back into the circulation in high-density lipoprotein (HDL) particles. At affected sites in the intima, cholesterol accumulates in deposits known as atheromas. These local accumulations are due to disturbances in the cholesterol flow through the intima, resulting in imbalance between inflow and outflow of cholesterol. The rate of cholesterol accumulation depends ultimately on the severity of the imbalance. The factor primarily responsible for this cholesterol imbalance appears to be local modification of LDL particles. Hence, to prevent accumulation of cholesterol in the intima, the production of modified LDL particles must be prevented. This can best be achieved by reducing the inflow of LDL particles into the intima. This, in turn, can be achieved by lowering the concentration of circulating LDL particles. In addition, increasing the concentration of circulating HDL particles should accelerate the rate of removal of cholesterol from the intima, so further improving the disturbed cholesterol balance at the atheromatous sites.