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Comprehensive targeted and non-targeted lipidomics analyses in failing and non-failing heart
Ganesh V Halade1, Anela Dorbane2, Kevin A Ingle3
1Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, 703 19th Street South, MC7755, Birmingham, AL, 35294, USA. ganeshhalade@uabmc.edu.
Insights
Myocardial infarction triggers inflammation and the formation of lipid-resolving molecules in the heart. These bioactive lipids are crucial for resolving inflammation and improving heart failure post-infarction.
Area of Science:
- Cardiovascular Biology
- Lipidomics
- Inflammation Research
Background:
- Myocardial infarction (MI) and heart failure are leading global causes of death.
- The precise mechanisms underlying post-MI heart failure pathology remain incompletely understood.
- Inflammatory responses play a critical role in cardiac injury and repair post-MI.
Purpose of the Study:
- To investigate the role of bioactive lipid-resolving molecules at the site of myocardial injury post-MI.
- To test the hypothesis that inflammation resolution involves specific lipid mediators in acute heart failure.
- To characterize the spatial distribution and changes in cardiac lipids following myocardial infarction.
Main Methods:
- Induction of myocardial infarction using a permanent coronary ligation model in rodents.
- Mass spectrometry imaging (MSI) in positive and negative ionization modes to analyze lipid distribution.
- Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for lipid structure confirmation.
- Principal component analysis (PCA) for comprehensive visualization of lipid profile alterations.
Main Results:
- MI induced decreased contractility, wall thinning, and necrosis in the left ventricle.
- MSI detected inflammation-resolving bioactive molecules (e.g., resolvins) and phosphatidylcholines in the infarcted myocardium.
- Significant increases in resolvin lipids and comprehensive lipid remodeling were observed at the infarction site.
- Lipid profiles differed significantly between MI and non-MI hearts.
Conclusions:
- The infarcted myocardium is a key site for inflammation-resolution pathomechanics.
- Bioactive lipid-resolving molecules are critical for resolving inflammation and mitigating heart failure pathophysiology post-MI.
- Lipidomic analysis provides crucial insights into the molecular mechanisms of cardiac injury and repair.
Abstract:
Myocardial infarction (MI) and subsequent progressive heart failure pathology is the major cause of death worldwide; however, the mechanism of this pathology remains unclear. The present work aimed at testing the hypothesis whether the inflammatory response is superimposed with the formation of bioactive lipid resolving molecules at the site of the injured myocardium in acute heart failure pathology post-MI. In this view, we used a robust permanent coronary ligation model to induce MI, leading to decreased contractility index with marked wall thinning and necrosis of the infarcted left ventricle. Then, we applied mass spectrometry imaging (MSI) in positive and negative ionization modes to characterize the spatial distribution of left ventricle lipids in the infarcted myocardium post-MI. After micro-extraction, liquid chromatography coupled to tandem mass spectrometry was used to confirm the structures of the imaged lipids. Statistical tools such as principal component analysis were used to establish a comprehensive visualization of lipid profile changes in MI and no-MI hearts. Resolving bioactive molecules such as resolvin (Rv) D1, RvD5, RvE3, 17-HDHA, LXA4, and 18-HEPE were detected in negative ion mode MSI, whereas phosphatidyl cholines (PC) and oxidized derivatives thereof were detected in positive ion mode. MSI-based analysis demonstrated a significant increase in resolvin bioactive lipids with comprehensive lipid remodeling at the site of infarction. These results clearly indicate that infarcted myocardium is the primary location of inflammation-resolution pathomechanics which is critical for resolution of inflammation and heart failure pathophysiology. Graphical abstract Applied scheme to determine comprehensive lipidomics in failing and non-failing heart.
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