Distinct Fatty Acid Compositions of HDL Phospholipids Are Characteristic of Metabolic Syndrome and Premature Coronary Heart Disease-Family Study.

HDL particles can be structurally modified in atherosclerotic disorders associated with low HDL cholesterol level (HDL-C). We studied whether the lipidome of the main phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin (SM) species of HDL2 and HDL3 subfractions is associated with premature coronary heart disease (CHD) or metabolic syndrome (MetS) in families where common low HDL-C predisposes to premature CHD. The lipidome was analyzed by LC-MS. Lysophosphatidylcholines were depleted of linoleic acid relative to more saturated and shorter-chained acids containing species in MetS compared with non-affected subjects: the ratio of palmitic to linoleic acid was elevated by more than 30%. A minor PC (16:0/16:1) was elevated (28-40%) in MetS. The contents of oleic acid containing PCs were elevated relative to linoleic acid containing PCs in MetS; the ratio of PC (16:0/18:1) to PC (16:0/18:2) was elevated by 11-16%. Certain PC and SM ratios, e.g., PC (18:0/20:3) to PC (16:0/18:2) and a minor SM 36:2 to an abundant SM 34:1, were higher (11-36%) in MetS and CHD. The fatty acid composition of certain LPCs and PCs displayed a characteristic pattern in MetS, enriched with palmitic, palmitoleic or oleic acids relative to linoleic acid. Certain PC and SM ratios related consistently to CHD and MetS.

Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level.

OBJECTIVE: The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. METHODS: HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. RESULTS: While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001). CONCLUSION: Our results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed.

Plasma levels of antibodies against oxidized LDL are inherited but not associated with HDL-cholesterol level in families with early coronary heart disease.

OBJECTIVE: Oxidized low-density lipoproteins (oxLDL) and antibodies against them (anti-oxLDLs) are thought to play a central role in atherosclerosis. One proposed antiatherosclerotic mechanism for HDL is to prevent oxidation of LDL. This study examined whether plasma HDL-cholesterol (HDL-C) is related to plasma anti-oxLDL levels. METHODS: We collected families based on probands with low HDL-C and premature coronary heart disease (CHD). Antibody levels were determined in samples from 405 subjects. Immunoglobulin G, M and A levels against two in vitro models of oxLDL, malondialdehyde-acetaldehyde-modified LDL (MAA-LDL) and copper oxidized LDL (CuOx-LDL), were measured by ELISA. We carried out heritability estimation of antibody traits and bivariate analyses between HDL-C, LDL-C and antibody traits. RESULTS: All the antibody levels were significantly inherited (p < 0.001), heritability estimates ranging from 0.28 to 0.65. HDL-C exhibited no environmental or genetic cross-correlations with antibody levels. Significant environmental correlations were detected between LDL-C and both IgG levels (ρ(E) = 0.40, p = 0.046 and ρ(E) = 0.39, p < 0.001). There were no differences in antibody levels between subjects with normal and low HDL-C, or between CHD-affected and non-affected subjects. CONCLUSION: In this study, low HDL-C level displayed no significant associations with the anti-oxLDL levels measured. The heritability of the anti-oxLDL levels was a novel and interesting finding.