Low-density lipoproteins isolated from the blood of patients with coronary heart disease induce the accumulation of lipids in human aortic cells.

Smooth muscle cells cultured from the intima of unaffected human aorta accumulate lipids during incubation with the blood serum of patients with coronary heart disease (CHD). Blood sera of most healthy subjects fail to induce the deposition of lipids in cultured cells. Very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins of two subclasses (HDL2 and HDL3) were isolated from the blood of healthy subjects and CHD patients. LDL from the blood of healthy individuals did not raise intracellular lipid levels within 24 hr of cultivation (the maximal concentration used, 1000 micrograms/ml). During the same incubation period, LDL obtained from the blood of CHD patients (200 to 1000 micrograms/ml) caused a 2- to 5-fold rise in cholesteryl esters as well as a 1.5- to 3-fold rise in free cholesterol and triglycerides, whereas intracellular phospholipid levels remained unchanged. There was a direct correlation (r = 0.95) between cholesterol accumulation in the cells incubated with whole sera of CHD patients and cholesterol level in the cells incubated with LDL isolated from these sera. In one of the three cases, the ability to raise the intracellular level of cholesteryl esters was demonstrated by VLDL (500 micrograms/ml) derived from CHD patients' blood. HDL2 and HDL3 did not affect lipid levels in smooth muscle cells cultured from unaffected intima. HDL3 from the blood of CHD patients and healthy subjects (50 to 250 micrograms/ml) reduced cholesteryl ester levels in cells cultured from atherosclerotic plaques 1.5- to 2-fold. HDL2 also decreased the content of cholesteryl esters in plaque cells, though less effectively than HDL3. The data obtained suggest that circulating LDL and, possibly, VLDL in the blood of CHD patients are capable of inducing the accumulation of fat in vascular wall cells.

Blood serum atherogenicity associated with coronary atherosclerosis. Evidence for nonlipid factor providing atherogenicity of low-density lipoproteins and an approach to its elimination.

To reveal the presence of atherogenic potential in the blood serum obtained from patients with angiographically assessed coronary atherosclerosis we used primary cultures of subendothelial cells isolated by collagenase from unaffected human aortic intima. Earlier, we have demonstrated that such cultures are made up mostly of typical and modified smooth muscle cells. Within 24 hours of cultivation with a 40% sera of patients suffering from coronary atherosclerosis, the total intracellular cholesterol level increased twofold to fivefold. Cultivation with the sera of healthy subjects had no effect on the intracellular cholesterol level. The sera of patients were separated by ultracentrifugation into two fractions: total lipoprotein fraction containing the main classes of lipoproteins and a lipoprotein-deficient fraction. The former, but not the lipoprotein-deficient fraction, was characterized by atherogenicity (i.e., the ability to induce the accumulation of intracellular cholesterol). Lipoproteins of the patients' serum were separated into main classes: low density lipoproteins (LDL), very low density lipoproteins (VLDL), and high density lipoproteins (HDL2 and HDL3). An atherogenic component of the serum capable of stimulating the deposition of intracellular cholesterol was represented by LDL and, in one case, by VLDL, but not by other classes of lipoproteins. LDL and other lipoproteins isolated from the blood serum of healthy subjects failed to raise the cholesterol content in cultured cells; that is, they were nonatherogenic.(ABSTRACT TRUNCATED AT 250 WORDS)