ApoCIII enrichment in HDL impairs HDL-mediated cholesterol efflux capacity

Abstract

Apolipoprotein CIII (apoCIII) has been reported to be tightly associated with triglyceride metabolism and the susceptibility to coronary artery disease (CAD). Besides, apoCIII has also been found to affect the anti-apoptotic effects of HDL. However, the effect of apoCIII on HDL-mediated cholesterol efflux, the crucial function of HDL, has not been reported. A hospital-based case-control study was conducted to compare the apoCIII distribution in lipoproteins between CAD patients and nonCAD controls and to explore the relationship between HDL-associated apoCIII (apoCIIIHDL) and HDL-mediated cholesterol efflux. One hundred forty CAD patients and nighty nine nonCAD controls were included. Plasma apoCIII, apoCIIIHDL and cholesterol efflux capacity was measured. The apoCIIIHDL ratio (apoCIIIHDL over plasma apoCIII) was significantly higher in CAD patients than that in control group (0.52 ± 0.24 vs. 0.43 ± 0.22, P = 0.004). Both apoCIIIHDL and apoCIIIHDL ratio were inversely correlated with cholesterol efflux capacity (r = −0.241, P = 0.0002; r = −0.318, P < 0.0001, respectively). Stepwise multiple regression analysis revealed that the apoCIIIHDL ratio was an independent contributor to HDL-mediated cholesterol efflux capacity (standardized β = −0.325, P < 0.001). This study indicates that the presence of apoCIII in HDL may affect HDL-mediated cholesterol efflux capacity, implying the alternative role of apoCIII in the atherogenesis.

Roles of cholesterol efflux capacity in the occurrence and prognosis coronary artery disease

“…Cholesterol efflux from macrophages is considered a crucial step of reverse cholesterol transport that is responsible for maintaining normal cholesterol balance. Previous study revealed that RCT had a strong inverse association with carotid intima-media thickness and CAD likelihood independent of HDL-C level [3]. Therefore, cholesterol efflux capacity reflects the global ability of cholesterol efflux from macrophages.…”

“…After excluding 166 other studies designed as case reports, letters to editor, review articles, in vitro studies, animal studies, 41 articles in full-text article were assessed for eligibility. Finally, 18 articles reporting outcomes of interest were included in the meta-analysis [2,3,7,8,10,[13][14][15][16][17][18][19][20][21][22][23][24][25]. Of them, 12 studies were designed as case-control studies and 6 were cohort studies.…”

“…Multiple epidemiological studies documented that CAD patients presented reduced high density lipoprotein-cholesterol (HDL-C) and HDL-C level negatively predicted the occurrence of CAD, which proposed a rational for raising HDL-C for the treatment of CAD [2]. Unfortunately, the clinical trials for evaluating the clinical efficacy of HDL-C raising therapeutics have ceased for not observing the priority of these drugs in reducing cardiovascular events [3]. Furthermore, it is considered that in normal healthy states, HDL exhibits anti-inflammatory, anti-oxidative and reverse cholesterol transport effects to resist atherosclerosis.…”

Novel Associations between Related Proteins and Cellular Effects of High-Density Lipoprotein

“…Gordon et al 9) and Pamir et al 10) identified several porteins such as apoA1, Gelsolin, antithrombin-III, apoE, and plasminogen as determinants of this capacity. Some proteins including complement C3 9) or apoC3 11) showed negative relationships to cholesterol efflux capacity. However, the relationships have not been consistent among all studies.…”

Evacetrapib and cardiovascular outcomes: reasons for lack of efficacy

“…It has been suggested that drug-associated larger HDL particles can provide increase amounts of apolipoprotein CIII to the arterial wall. Furthermore, apolipoprotein CIIIenriched HDL particles have been shown to exhibit less functional activity (that is impairment of HDL-mediated cholesterol efflux capacity) (16). It is worth mentioning that increased Apo E levels have been related with ischemic heart disease in men (17).…”