Affiliation:
1. Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, No. 49 North Garden Road, Haidian District, Beijing 100191, China
Abstract
Levels of high-density lipoprotein cholesterol (HDL-C) are inversely associated with the incidence of coronary artery disease (CAD). However, the underlying mechanism of CAD in the context of elevated HDL-C levels is unclear. Our study aimed to explore the lipid signatures in patients with CAD and elevated HDL-C levels and to identify potential diagnostic biomarkers for these conditions. We measured the plasma lipidomes of forty participants with elevated HDL-C levels (men with >50 mg/dL and women with >60 mg/dL), with or without CAD, using liquid chromatography–tandem mass spectrometry. We analyzed four hundred fifty-eight lipid species and identified an altered lipidomic profile in subjects with CAD and high HDL-C levels. In addition, we identified eighteen distinct lipid species, including eight sphingolipids and ten glycerophospholipids; all of these, except sphingosine-1-phosphate (d20:1), were higher in the CAD group. Pathways for sphingolipid and glycerophospholipid metabolism were the most significantly altered. Moreover, our data led to a diagnostic model with an area under the curve of 0.935, in which monosialo-dihexosyl ganglioside (GM3) (d18:1/22:0), GM3 (d18:0/22:0), and phosphatidylserine (38:4) were combined. We found that a characteristic lipidome signature is associated with CAD in individuals with elevated HDL-C levels. Additionally, the disorders of sphingolipid as well as glycerophospholipid metabolism may underlie CAD.
Funder
University of Michigan-Peking University Joint Institute for Translational and Clinical Research
National Natural Science Foundation of China
Beijing Natural Science Foundation
Subject
Molecular Biology,Biochemistry,Endocrinology, Diabetes and Metabolism
Reference47 articles.
1. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019;Roth;J. Am. Coll. Cardiol.,2020
2. A Review on Coronary Artery Disease, Its Risk Factors, and Therapeutics;Malakar;J. Cell Physiol.,2019
3. (2009). The Emerging Risk Factors Collaboration Major Lipids, Apolipoproteins, and Risk of Vascular Disease. JAMA, 302, 1993–2000.
4. Effects of Torcetrapib in Patients at High Risk for Coronary Events;Barter;N. Engl. J. Med.,2007
5. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease;Lincoff;N. Engl. J. Med.,2017