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.

We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.

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)