Direct estimation of HDL-mediated cholesterol efflux capacity from serum

Abstract

High-density lipoprotein mediated cholesterol efflux capacity (HDL-CEC) is a functional attribute that may have a protective role in atherogenesis. However, the estimation of HDL-CEC is based on in vitro cell assays that are laborious and hamper large-scale phenotyping. Here, we present a cost-effective high-throughput nuclear magnetic resonance (NMR) spectroscopy method to estimate HDL-CEC directly from serum. We applied the new method in a population-based study of 7,603 individuals including 574 who developed incident coronary heart disease (CHD) during 15 years of follow-up, making this the largest quantitative study for HDL-CEC. As estimated by NMR-spectroscopy, a 1-SD higher HDL-CEC was associated with a lower risk of incident CHD (hazards ratio 0.86; 95%CI 0.79-0.93, adjusted for traditional risk factors and HDL-C). These findings are consistent with published associations based on in vitro cell assays. These corroborative large-scale findings provide further support for a potential protective role of HDL-CEC in CHD, and substantiate this new method and its future applications.

Apolipoprotein A-I concentrations and risk of coronary artery disease: A Mendelian randomization study

“…However, the rationale behind apoA-I-infusion therapies is that increases in apoA-I ought to promote cholesterol efflux from arterial wall macrophages, a process that can be quantitatively measured by HDL cholesterol efflux capacity (HDL-CEC). Similar to HDL cholesterol and apoA-I, HDL-CEC is inversely associated with risk of CAD [6]. The AEGIS trial showed that apoA-I infusion therapy with CSL112 led to higher concentrations of apoA-I and higher HDL-CEC [15,18], which suggests that higher HDL-CEC may represent a target-mediated effect of elevations in apoA-I.…”

“…However, it remains feasible that other aspects of HDL, such as the functional attributes of HDL particles, might have atheroprotective effects. The ability of HDL particles to extract cholesterol from lipid-laden cells, socalled cholesterol efflux, has recently emerged as the most prominent new measure for HDL-related atheroprotectivity [6]. Apolipoprotein A-I (apoA-I) is a key functional apolipoprotein component of HDL particles and plays a central role in cholesterol efflux [7].This has led to anticipation that modification of circulating apoA-I might represent a novel therapeutic approach to the treatment and prevention of CAD.…”

High density lipoprotein functionality and cardiovascular events and mortality: A systematic review and meta-analysis

“…Moreover, preactivation of cells to enhance ABC transporter expression increases the proportion of efflux through them [67]. In this regard, new cost and time-effective methodologies that are not cell-based are being developed that have the potential to overcome these technical issues [68]. Despite differences in the determination of cholesterol efflux capacity, the majority of studies reported a negative association with cardiovascular disease risk, regardless of the technique employed, as shown in the stratified analysis.…”

Effect of Katakakhadiradi Kashayam on Lipid Profile and Pancreatic Damage in Type II Diabetes Mellitus

“…In a Shimadzu UV spectrophotometer, the optical density was taken (530 nm after 20 minutes). The levels of cholesterol were measured in mg/dl [10].…”