Highlights
- •A first integrative study using human and murine hearts on association of lipids in heart failure was investigated.
- •Lipid fingerprinting led to the identification of 273 species in clinical and mouse samples.
- •A decrease in cardiac phosphatidylethanolamines is associated with human ischemic heart disease.
- •Inter-organ (heart, spleen, and kidney) and systemic lipid signatures were profiled in acute and chronic HF post-MI mice.
Abstract
Background and aims
Myocardial infarction (MI) is a leading cause of heart failure (HF). After MI, lipids
undergo several phasic changes implicated in cardiac repair if inflammation resolves
on time. However, if inflammation continues, that leads to end stage HF progression
and development. Numerous studies have analyzed the traditional risk factors; however,
temporal lipidomics data for human and animal models are limited. Thus, we aimed to
obtain sequential lipid profiling from acute to chronic HF.
Methods
Here, we report the comprehensive lipidome of the hearts from diseased and healthy
subjects. To induce heart failure in mice, we used a non-reperfused model of coronary
ligation, and MI was confirmed by echocardiography and histology, then temporal kinetics
of lipids in different tissues (heart, spleen, kidney), and plasma was quantitated
from heart failure mice and compared with naïve controls. For lipid analysis in mouse
and human samples, untargeted liquid chromatography-linear trap quadrupole orbitrap
mass spectrometry (LC-LTQ-Orbitrap MS) was performed.
Results
In humans, multivariate analysis revealed distinct cardiac lipid profiles between
healthy and ischemic subjects, with 16 lipid species significantly downregulated by
5-fold, mainly phosphatidylethanolamines (PE), in the ischemic heart. In contrast,
PE levels were markedly increased in mouse tissues and plasma in chronic MI, indicating
possible cardiac remodeling. Further, fold change analysis revealed site-specific
lipid biomarkers for acute and chronic HF. A significant decrease in sulfatides (SHexCer
(34:1; 2O)) and sphingomyelins (SM (d18:1/16:0)) was observed in mouse tissues and
plasma in chronic HF.
Conclusions
Overall, a significant decreased lipidome in human ischemic LV and differential lipid
metabolites in the transition of acute to chronic HF with inter-organ communication
could provide novel insights into targeting integrative pathways for the early diagnosis
or development of novel therapeutics to delay/prevent HF.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: November 09, 2022
Accepted:
November 3,
2022
Received in revised form:
October 18,
2022
Received:
June 30,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
