Abstract 11924: Plasma 27-hydroxycholesterol/cholesterol Ratio is Increased in Low High Density Lipoprotein-Cholesterol Healthy Subjects

Abstract

Low HDL-C is associated with an increased risk of cardiovascular disease. HDL plays antiatherogenic functions that include its role in the reverse cholesterol transport. The cholesterol efflux mediated by HDL, transfers the excess of cellular cholesterol to the liver being excreted by bile acids. The production of the 27-hydroxycholesterol (27OHC) by extrahepatic tissues and its transport to the liver may be an alternative pathway of reverse cholesterol transport. The cholesterol is converted into 27OHC by sterol 27-hydroxylase, an enzyme which is widely distributed among tissues, but expressed at high activity in vascular endothelium and macrophages. There is a continuous flux of this oxysterol from the tissues to the liver, where it is converted into bile acids.

Objective: Measure plasma concentrations of 27OHC in subjects that differ according to their plasma HDL-C concentration.

Methods: Healthy men presenting low HDL-C (< 40mg/dL), n=18 or high HDL-C (>60 mg/d), n=18, BMI < 30kg/m², were recruited after excluding secondary causes that might interfere their plasma lipid concentrations such as smoking, heavy drinking and diabetes. Blood samples were drawn after a 12h fasting period for the measurement of 27OHC by the combined GLC/MS analysis utilizing deuterium-label internal standard.

Results: Anthropometric data, plasma levels (mg/dL) of cholesterol, HDL-C, LDL-C (calculated by the Friedewald formula), triglycerides, glucose, 27OHC (ng/mL) (means ± SD, unpaired Student’s t test) and 27OHC/cholesterol ratio (medians and ranges, Mann Whitney test) in low HDL-C and high HDL-C groups are shown in the table.

Conclusion: The data show a high 27OHC/cholesterol ratio in plasma of low HDL-C as compared to high HDL-C subjects, suggesting an increase of cholesterol excretion. This pathway could protect the cells against cholesterol accumulation, an alternative mechanism for the reverse cholesterol transport in individuals with low HDL concentration.