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Updated: Jan 26, 2026
Gene Transfer for Ischemic Heart Failure in a Preclinical Model
Published on: May 15, 2011
Lipoxygenase drives lipidomic and metabolic reprogramming in ischemic heart failure
Ganesh V Halade1, Vasundhara Kain1, Bochra Tourki1
1Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, AL, United States.
Insights
Lipoxygenase deficiency in mice improved cardiac healing after myocardial infarction (MI) by altering lipid metabolism and reducing inflammation, leading to better survival in heart failure (HF). This highlights lipoxygenase
Area of Science:
- Cardiovascular Biology
- Metabolomics
- Lipidomics
Background:
- Delayed cardiac remodeling post-myocardial infarction (MI) is crucial for preventing chronic heart failure (HF).
- The temporal dynamics of lipidomic and metabolic signaling in HF remain poorly understood.
- Consensus on metabolic and lipidomic signatures influencing cardiac structure, function, and survival in HF is lacking.
Purpose of the Study:
- To delineate lipidomic and metabolic changes in ischemic heart failure (HF) using a genetic knockout model.
- To define the role of lipoxygenase in the temporal kinetics of metabolic and lipidomic reprogramming in HF.
- To investigate the impact of lipoxygenase on leukocyte activation and non-resolving inflammation in HF.
Main Methods:
- Utilized a permanent coronary ligation mouse model to induce MI and study acute and chronic HF.
- Quantitated systemic metabolic changes and performed lipidomic profiling in infarcted heart tissue.
- Analyzed lipoxygenase-derived specialized pro-resolving mediators in lipoxygenase-deficient (12/15LOX-/-) mice.
Main Results:
- Lipoxygenase-deficient mice showed altered biosynthesis of epoxyeicosatrienoic acids (EETs), facilitating cardiac healing.
- These mice exhibited reduced levels of the diabetes risk biomarker 2-aminoadipic acid.
- Profound alterations in plasma metabolic signaling (hexoses, amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingolipids) were observed, improving survival in acute HF.
Conclusions:
- Specific lipoxygenase deletion modifies lipidomic and metabolic signatures, impacting leukocyte profiles.
- These alterations delay HF progression and enhance survival.
- Further research is needed to elucidate the molecular network of lipidome and metabolome in human HF.
Background:
After myocardial infarction (MI), delayed progression or reversal of cardiac remodeling is a prime target to limit advanced chronic heart failure (HF). However, the temporal kinetics of lipidomic and systemic metabolic signaling is unclear in HF. There is no consensus on metabolic and lipidomic signatures that influence structure, function, and survival in HF. Here we use genetic knock out model to delineate lipidomic, and metabolic changes to describe the role of lipoxygenase in advancing ischemic HF driven by leukocyte activation with signs of non-resolving inflammation. Bioactive lipids and metabolites are implicated in acute and chronic HF, and the goal of this study was to define the role of lipoxygenase in temporal kinetics of lipidomic and metabolic reprogramming in HF.
Materials And Methods:
To address this question, we used a permanent coronary ligation mouse model which showed profound metabolic and lipidomic reprogramming in acute HF. Additionally, we defined the lipoxygenase-mediated changes in cardiac pathophysiology in acute and chronic HF. For this, we quantitated systemic metabolic changes and lipidomic profiling in infarcted heart tissue with obvious structural remodeling and cardiac dysfunction progressing from acute to chronic HF in the survival cohort.
Results:
After MI, lipoxygenase-derived specialized pro-resolving mediators were quantitated and showed lipoxygenase-deficient mice (12/15LOX-/-) biosynthesize epoxyeicosatrienoic acid (EETs; cypoxins) to facilitate cardiac healing. Lipoxygenase-deficient mice reduced diabetes risk biomarker 2-aminoadipic acid with profound alterations of plasma metabolic signaling of hexoses, amino acids, biogenic amines, acylcarnitines, glycerophospholipids, and sphingolipids in acute HF, thereby improved survival.
Conclusion:
Specific lipoxygenase deletion alters lipidomic and metabolic signatures, with modified leukocyte profiling that delayed HF progression and improved survival. Future studies are warranted to define the molecular network of lipidome and metabolome in acute and chronic HF patients.
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