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Updated: Aug 19, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts
Siddabasave Gowda B Gowda1, Divyavani Gowda2, Fengjue Hou2
1Hokkaido University, Kita-12 Nishi-5, Kita-Ku, Sapporo, 060-0812, Japan; Graduate School of Global Food Resources, Hokkaido University, Kita-12 Nishi-5, Kita-Ku, Sapporo, 060-0812, Japan.
Insights
Lipid changes after heart attack (myocardial infarction) differ between humans and mice. This study reveals key lipid biomarkers for heart failure progression, offering new diagnostic and therapeutic targets.
Area of Science:
- Cardiovascular Science
- Lipidomics
- Biochemistry
Background:
- Myocardial infarction (MI) is a primary cause of heart failure (HF).
- Lipid changes post-MI are crucial for cardiac repair, but persistent inflammation drives HF progression.
- Limited temporal lipidomics data exist for human and animal models of HF.
Purpose of the Study:
- To perform sequential lipid profiling from acute to chronic heart failure.
- To analyze temporal lipidomics in human and mouse models of MI-induced HF.
- To identify lipid biomarkers associated with HF progression.
Main Methods:
- Comprehensive cardiac lipidome analysis in diseased and healthy subjects.
- Induction of non-reperfused MI in mice via coronary ligation, confirmed by echocardiography and histology.
- Untargeted liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (LC-LTQ-Orbitrap MS) for temporal lipid quantitation in mouse tissues and plasma compared to controls.
Main Results:
- Human ischemic hearts showed significantly downregulated phosphatidylethanolamines (PE) (≥5-fold).
- Mouse models exhibited increased PE levels in tissues and plasma during chronic MI, suggesting cardiac remodeling.
- Decreased sulfatides and sphingomyelins were observed in mouse tissues and plasma in chronic HF, indicating site-specific biomarkers.
Conclusions:
- A decreased cardiac lipidome in human ischemic left ventricles was observed.
- Differential lipid metabolites and inter-organ communication were identified during the transition from acute to chronic HF.
- Findings offer novel insights for early HF diagnosis and therapeutic strategies targeting integrative pathways.
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.
