Cholesterol Uptake Capacity: A New Measure of HDL Functionality for Coronary Risk Assessment. (15th October 2019)

• Record Type: Journal Article
• Authors: Harada, Amane; Toh, Ryuji; Murakami, Katsuhiro; Kiriyama, Maria; Yoshikawa, Keiko; Miwa, Keiko; Kubo, Takuya; Irino, Yasuhiro; Mori, Kenta; Tanaka, Nobuaki; Nishimura, Kunihiro; Ishida, Tatsuro; Hirata, Ken-ichi
• Is Part Of: Journal of applied laboratory medicine. Volume 2:Number 2(2017)
• Page Start: 186
• Page End: 200
• Publication Date: 2019-10-15
• Subjects: Clinical chemistry -- Periodicals; Diagnosis, Laboratory -- Periodicals; 616.0756
• DOI: 10.1373/jalm.2016.022913
• Languages: English
• ISSNs: 2576-9456

Abstract

Abstract: Background: Recent studies have shown that the cholesterol efflux capacity of HDL is a better predictor of cardiovascular disease (CVD) than HDL cholesterol. However, the standard procedures used for measuring cholesterol efflux capacity involve radioisotope-labeled cholesterol and cultured macrophages. Thus, a simpler method to measure HDL functionality is needed for clinical application. Methods: We established a cell-free assay system to evaluate the capacity of HDL to accept additional cholesterol, which we named cholesterol "uptake capacity, " using fluorescently labeled cholesterol and an anti-apolipoprotein A1 antibody. We quantified cholesterol uptake capacity of apolipoprotein B (apoB)-depleted serum samples from patients with coronary artery disease who had previously undergone revascularization. Results: This assay system exhibited high reproducibility (CV <10%) and a short processing time (<6 h). The myeloperoxidase-mediated oxidation of apoB-depleted serum impaired cholesterol uptake capacity. Cholesterol uptake capacity correlated significantly with cholesterol efflux capacity ( r 2 = 0.47, n = 30). Furthermore, cholesterol uptake capacity correlated inversely with the requirement for revascularization because of recurrence of coronary lesions in patients with optimal control of LDL cholesterol ( P < 0.01, n = 156). A multivariate analysis adjusted for traditional coronary risk factors showed that only cholesterol uptake capacity remained significant (odds ratio, 0.48; 95% CI, 0.29–0.80; P = 0.0048). Conclusions: Cholesterol uptake capacity assay evaluates the functionality of HDL in a sensitive and high-throughput manner without using radioisotope label and cells. This assay system could be used for the assessment of CVD risk in the clinical settings.