Cholesterol Uptake Capacity, a New Indicator of HDL Functionality, for Cardiovascular Risk Stratification in the Real World. Interview with:
Amane Harada, PhD
Senior Researcher
Central Research Laboratories, Sysmex Corporation
Kobe, Japan

Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD
Associate Professor
Division of Evidence-based Laboratory Medicine
Kobe University Graduate School of Medicine
Kobe, Japan What is the background for this study?

Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions.

Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease.

However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical.

To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”. What are the main findings?

Response: The procedures of our assay system is as follows; After removing apolipoprotein B-containing lipoprotein using polyethylene glycol, serum is incubated with fluorescence-labeled cholesterol, the HDL is captured by specific antibody for apoAI coated on a microplate, and then the amount of the labeled cholesterol in the HDL is measured using a plate reader. Thus, this assay system does not require radiolabeling and cells, and the procedures are simple.

This assay system exhibited high reproducibility (CV < 10%) and a short processing time (< 6 h). Cholesterol uptake capacity showed a good linear relationship with cholesterol efflux capacity. When HDL was oxidized by myeloperoxidase, we found a decrease in cholesterol uptake capacity, indicating that our new assay system can reflect HDL functionality.

We also analyzed the clinical performance of our assay system. We found that cholesterol uptake capacity correlated inversely with the recurrence of coronary artery disease in patients with optimal control of low-density lipoprotein cholesterol What should clinicians and patients take away from your report? What recommendations do you have for future research as a result of this study?

Response: Cholesterol uptake capacity assay allows evaluating the functionality of HDL in a sensitive and high-throughput manner without using radioisotope-label and cells. We believe that this assay system could be useful for validating the impact of “dysfunctional” HDL on cardiovascular risk stratification in the “Real World”. Thank you for your contribution to the community.


Amane Harada, Ryuji Toh, Katsuhiro Murakami, Maria Kiriyama, Keiko Yoshikawa, Keiko Miwa, Takuya Kubo, Yasuhiro Irino, Kenta Mori, Nobuaki Tanaka, Kunihiro Nishimura, Tatsuro Ishida, Ken-ichi Hirata. Cholesterol Uptake Capacity: A New Measure of HDL Functionality for Coronary Risk Assessment. Journal of Applied Laboratory Medicine, June 2017 DOI: 10.1373/jalm.2016.022913




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Last Updated on June 12, 2017 by Marie Benz MD FAAD