Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients
Hsiang-Yu Tang,
Chao-Hung Wang,
Hung-Yao Ho,
Pei-Ting Wu,
Chun-Ling Hung,
Cheng-Yu Huang,
Pei-Ru Wu,
Yung-Hsin Yeh,
Mei-Ling Cheng
Affiliations
Hsiang-Yu Tang
Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan Taiwan
Chao-Hung Wang
Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
Hung-Yao Ho
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Clinical Phenome Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Pei-Ting Wu
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Chun-Ling Hung
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Cheng-Yu Huang
Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan Taiwan
Pei-Ru Wu
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Yung-Hsin Yeh
Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Chang-Gung University, Taiwan
Mei-Ling Cheng
Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan Taiwan; Clinical Phenome Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Correspondence to: Department of Biomedical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33302, Taiwan (R.O.C.).
Lipids play an important role in the pathogenesis of cardiovascular disease. Changes in lipids of erythrocytes are indicative of the outcome of pathophysiological processes. In the present study, we assessed whether the lipid profiles of erythrocytes from heart failure (HF) patients are informative of their disease risk. The lipidomes of erythrocytes from 10 control subjects and 29 patients at different HF stages were analyzed using liquid chromatography time-of-flight mass spectrometry. The lipid composition of erythrocytes obtained from HF patients was significantly different from that of normal controls. The levels of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and sphingomyelins decreased in HF erythrocytes as compared with those of control subjects; however, the levels of lysoPCs, lysoPEs, and ceramides increased in HF erythrocytes. Notably, the oxidized cholesterol 7-ketocholesterol (7KCh) accumulated to higher level in HF erythrocytes than in plasma from the same patients. We further validated our findings with a cohort of 115 subjects of control subjects (n=28) and patients (n=87). Mechanistically, 7KCh promoted reactive oxygen species (ROS) formation in cardiomyocytes; and induced their death, probably through an ATF4-dependent pathway. Our findings suggest that erythrocytic 7KCh can be a risk factor for HF, and is probably implicated in its pathophysiology. Keywords: Heart failure, Lipidomics, 7-ketocholesterol, Oxidative stress
