Autoantibodies against modified low density lipoprotein. Nonlipid factor of blood plasma that stimulates foam cell formation.

Abstract

The blood serum of patients with coronary atherosclerosis possesses an ability to induce the accumulation of cellular lipids in primary cultures of human aortic intimal cells. Factors responsible for this property of the atherosclerotic patients' sera are represented by modified (desialylated) low density lipoprotein (LDL) and a nonlipid factor interacting with LDL. It was assumed that the nonlipid factor was antibodies against LDL. Total immunoglobulin G (IgG) fraction was isolated from the sera of atherosclerotic patients, and IgGs interacting with LDL (anti-LDL) were then purified by affinity chromatography on a sorbent with immobilized LDL. From the sera of patients, a 30-fold greater amount of anti-LDL has been isolated than from the sera of healthy donors. The affinity constant of anti-LDL to the lipoprotein obtained from the blood of healthy donors was 2 x 10(7) M-1. The affinity of anti-LDL to the lipoprotein from the blood of atherosclerotic patients, as well as to LDL desialylated in vitro with neuraminidase, was much higher. Anti-LDL increased the uptake of LDL by cultured aortic cells by approximately 2.5-fold and substantially increased intracellular lipid accumulation. The obtained data suggest that autoantibodies against LDL are an essential factor of blood plasma responsible for its atherogenic potential.