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
Rok vydání: 2017
Předmět:
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