Impaired HDL (High-Density Lipoprotein)-Mediated Macrophage Cholesterol Efflux in Patients With Abdominal Aortic Aneurysm—Brief Report

Abstract

Objective— The ability of HDL (high-density lipoprotein) to promote macrophage cholesterol efflux is considered the main HDL cardioprotective function. Abdominal aortic aneurysm (AAA) is usually characterized by cholesterol accumulation and macrophage infiltration in the aortic wall. Here, we aim to evaluate the composition of circulating HDL particles and their potential for promoting macrophage cholesterol efflux in AAA subjects. Approach and Results— First, we randomly selected AAA and control subjects from Spain. The AAA patients in the Spanish cohort showed lower plasma apoA-I levels concomitantly associated with low levels of plasma HDL cholesterol and the amount of preβ-HDL particles. We determined macrophage cholesterol efflux to apoB-depleted plasma, which contains mature HDL, preβ-HDL particles and HDL regulatory proteins. ApoB-depleted plasma from AAA patients displayed an impaired ability to promote macrophage cholesterol efflux. Next, we replicated the experiments with AAA and control subjects derived from Danish cohort. Danish AAA patients also showed lower apoA-I levels and a defective HDL-mediated macrophage cholesterol efflux. Conclusions— AAA patients show impaired HDL-facilitated cholesterol removal from macrophages, which could be mechanistically linked to AAA.

Macrophage Cholesterol Efflux Downregulation Is Not Associated with Abdominal Aortic Aneurysm (AAA) Progression

“…Recent reports support the concept that lipoproteins play a role in the pathogenesis of AAAs [14,15,21]. In agreement with our previous results in AAA subjects with large AAA diameter, LDLc and apoA-I were downregulated in the late stages of the disease [18]. However, cholesterol transported by HDL did not change and it is not considered a good surrogate marker of the lipoprotein antiatherogenicity.…”

“…No differences among the groups were observed in terms of smoking habits, diabetes, arterial hypertension, a history of cardiovascular events, use of statins and use of low-dose aspirin. As previously reported [16,18], the apoA-I concentrations in the AAA patients at presentation were significantly lower than those in the control group. Only patients with large size AAAs presented with significantly lower total cholesterol concentrations as compared with those in the control group, and this was concomitant with lower concentrations of LDL cholesterol.…”

“…However, cholesterol transported by HDL did not change and it is not considered a good surrogate marker of the lipoprotein antiatherogenicity. We recently demonstrated that that HDL-facilitated MCE, one of the potential main surrogate markers of HDL function, was impaired in large size AAA patients [18]. In this study, in a larger cohort of AAA patients, we confirmed that HDL-facilitated MCE was downregulated in large size AAA patients compared with that of controls and small/medium size AAA patients.…”

“…We recently reported that AAA patients showed impaired HDL-mediated MCE, which could be mechanistically linked to AAA. This inverse association was confirmed after adjusting for age, statin use, plasma lipids, apoA-I and HDLc levels [18]. However, this study included only AAA patients with a large aortic diameter (>50 mm).…”

“…The MCE capacity of apoB-depleted plasma samples (equivalent to 5% of plasma containing mature HDL, nascent preβ-HDL particles and HDL regulatory proteins) was determined using J774.A1 [ 3 H]-cholesterol-labeled murine macrophages according to a previously described protocol [18,20]. Briefly, macrophages were seeded and grown for two days in the Roswell Park Memorial Institute (RPMI) growth medium.…”