Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients
Autor: | Hung-Yao Ho, Yung-Hsin Yeh, Cheng-Yu Huang, Mei-Ling Cheng, Pei-Ting Wu, Chao-Hung Wang, Chun-Ling Hung, Pei-Ru Wu, Hsiang-Yu Tang |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Erythrocytes Clinical Biochemistry 030204 cardiovascular system & hematology Biology medicine.disease_cause Biochemistry Pathogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Lipidomics medicine Humans lcsh:QH301-705.5 Ketocholesterols 7-ketocholesterol Aged chemistry.chemical_classification Heart Failure lcsh:R5-920 Reactive oxygen species Cholesterol Organic Chemistry Middle Aged medicine.disease Pathophysiology Oxidative Stress 030104 developmental biology Endocrinology lcsh:Biology (General) chemistry Heart failure Immunology Female lcsh:Medicine (General) Sphingomyelin Reactive Oxygen Species Oxidation-Reduction Oxidative stress Research Paper |
Zdroj: | Redox Biology Redox Biology, Vol 14, Iss, Pp 499-508 (2018) |
ISSN: | 2213-2317 |
Popis: | 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 |
Databáze: | OpenAIRE |
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