The Relationship Between High-density Lipoprotein Cholesterol And The Function Of Cardiovascular And Kidney

Objective:High-density lipoprotein cholesterol (HDL-C), as one of the most important cardiovascular risk factors, was found to be a reliable cardiovascular indicator in patients with advanced chronic kidney disease. But the relationship between HDL-C and the renal function in general population is still unclear. Arterial stiffness is another risk factor for renal disease, its association with HDL-C in the elderly population is indefinite. To investigate the relationship between HDL-C and arterial stiffness can be used to explain the relationship which may exist between HDL-C and renal function, but cannot determine a causal link. D-4F, an apolipoprotein AI mimetic peptide, has recently been widespread reported with the advantage of low production cost and oral administration effects. D-4F intervention can clear causal relationship between HDL-C and the function of cardiovascular and kidney.Methods:To evaluate the correlation between HDL-C levels and estimated glomerular filtration rate (eGFR) in a community population of4925individuals, univariate analyses and multivariable linear regression analysis were performed. We also related serum levels of HDL-C and other cardiovascular risk factors such as homocysteine to two measures of arterial stiffness [carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV] in780elderly participants. Ldlr-/-mice with long-term high cholesterol diet were treated with different doses of D-4F in drinking water, the structure and function of heart was determined by ultrasound biomicroscopy. Kidneys and hearts were harvested and examined for histological characteristics.Results:1. After adjustment for some confounding factors, HDL-C level was independently associated with all quartiles of eGFR in the general population;2. In elderly people, HDL-C level was inversely proportional with aortic stiffness, HDL-C level and homocysteine level was also negatively correlated, an association between homocysteine level and aortic stiffness was founded, too;3. High fat and high cholesterol-fed Ldlr-/-mice with D-4F oral treatment showed a dose-dependent reduction in weight and the level of lipid in heart and kidney, low dose of D-4F can be significantly improved cardiac structure and function, the protective effect of D-4F to kidney was gradually increased with increasing dose.Conclusion:In community survey we found that low HDL-C level was associated with early changes of renal dysfunction, which may be related with the weakened protective effect of HDL on aortic arterial stiffness. In animal experiment we observed that D-4F can reduce the weight of high cholesterol-fed mice and protect their heart and kidney tissue, which suggest the beneficial role of HDL-C to cardiovascular and kidney.