Cholesterol efflux capacity of high-density lipoprotein (HDL) particles is impaired in age-related macular degeneration patients with high plasma HDL-cholesterol levels

Abstract

Purpose : Epidemiological studies demonstrated an association between elevated plasma high-density lipoprotein-cholesterol (HDL-c) levels and AMD. This is in contrast to the negative association of plasma HDL-c levels with the risk of cardiovascular disease. Apart from the statistical association, little is known with respect to the functional change of HDL in AMD patients. The capacity to mediate cellular cholesterol efflux is one of the major functions of HDL, followed by the transportation of cholesterol by HDL to the liver via a process called reverse cholesterol transport. Genetic studies identified genes associated with AMD, including ABCA1, CETP, LIPC and APOE that are also related to HDL-mediated cholesterol efflux. In accordance, we hypothesized that the cholesterol efflux capacity (CEC) of HDL is impaired in AMD patients, consequently leading to cholesterol accumulation underneath retinal pigment epithelium (RPE) cells, facilitating drusen formation.

Methods : To approach this, HDL was isolated from 30 AMD patients and 30 age-matched controls, and the capacity of HDL to mediate cellular cholesterol efflux from [³H]-cholesterol-loaded ARPE-19 cells was assessed by measuring the percentage of [³H]-cholesterol secreted into the culture medium. Unpaired T test and Mann-Whitney U test were used to assess the difference between patients and controls.

Results : We found no significant differences in CEC between AMD patients and controls when comparing HDL isolated from 1 ml of plasma from each individual. However, HDL from AMD patients with high, but not low plasma HDL-c levels, showed a decreased CEC (11.62%, p=0.027) per HDL particle as compared to healthy controls.

Conclusions : Together, our data suggest that impaired cholesterol efflux capacity of HDL is not causal for AMD pathogenesis but may be a result of other metabolic dysfunctions in AMD patients. Elevated plasma HDL-c levels in AMD patients might compensate for the decreased CEC per HDL particle.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.