Abstract
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.
Highlights
Cardiovascular disease is a major health problem and the leading cause of death globally
Patients with heart failure (HF) were classified as stages A, B, and C according to the American College of Cardiology and the American Heart Association Heart Failure (ACC/AHA HF) classification system [17]: patients in stage A were at high risk and asymptomatic but did not have structural heart disease; patients in stage B had structural heart disease but were asymptomatic; and patients in stage C had been hospitalized due to acute or decompensated chronic HF
7KCh, lysoPCs, lysoPEs, and ceramides significantly increased in abundance in HF erythrocytes, whereas the levels of PCs, PEs, and SMs significantly decreased
Summary
Cardiovascular disease is a major health problem and the leading cause of death globally. The pathogenic mechanism leading to this end stage is complicated. Several biochemical pathways, including the pentose phosphate pathway, anaplerotic metabolism, ketone body metabolism, lipotoxic intermediate metabolism, and glycolysis, are affected in patients with HF [3,4,5]. Changes in metabolites have been identified in plasma and are associated with clinical outcomes in patients with HF [6,7]. These findings suggest that metabolic remodeling in patients may occur during HF progression, and the metabolite profile can be used as a biomarker panel for a variety of assessment purposes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
