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Comprehensive targeted and non-targeted lipidomics analyses in failing and non-failing heart

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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.

Applied scheme to determine comprehensive lipidomics in failing and non-failing heart.

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Abbreviations

AA:

Arachidonic acid

AUC:

Area under curve

DHA:

Docosahexaenoic acid

EPA:

Eicosapentaenoic acid

FA:

Fatty acids

HDHA:

Hydroxydocosahexaenoic acid

HEPE:

Hydroxyeicosapentaenoic acid

HETEs:

Hydroperoxyeicosatetraenoic acid

LC-MS/MS:

Liquid chromatography-mass spectrometry

LMs:

Lipid mediators

LTs:

Leukotrienes

LV:

Left ventricle

LX:

Lipoxins

MALDI:

Matrix-assisted laser desorption ionization

MI:

Myocardial infarction

MRM:

Multiple reaction monitoring

MSI:

Molecular mass spectrometry imaging

PCA:

Principal component analysis

PL:

Phospholipids

Rv:

Resolvins

TX:

Thromboxane

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Acknowledgements

We acknowledge the support from National Institutes of Health [AT006704 and HL132989] and The University of Alabama at Birmingham (UAB) Pittman scholar award to GVH, American Heart Association postdoctoral fellowship POST31000008 to VK, and Idex program from University of Bordeaux, France, to BF.

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Authors and Affiliations

  1. Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, 703 19th Street South, MC7755, Birmingham, AL, 35294, USA

    Ganesh V. Halade, Kevin A. Ingle & Vasundhara Kain

  2. Chimie et Biologie des Membranes et Nanoobjets, University of Bordeaux, CNRS UMR 5248, 146, rue Léo Saignat, 33076, Bordeaux, France

    Anela Dorbane, Jean-Marie Schmitter & Boutayna Rhourri-Frih

Authors
  1. Ganesh V. Halade
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  2. Anela Dorbane
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  3. Kevin A. Ingle
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  4. Vasundhara Kain
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Correspondence to Ganesh V. Halade or Boutayna Rhourri-Frih.

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Halade, G.V., Dorbane, A., Ingle, K.A. et al. Comprehensive targeted and non-targeted lipidomics analyses in failing and non-failing heart. Anal Bioanal Chem 410, 1965–1976 (2018). https://doi.org/10.1007/s00216-018-0863-7

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  • DOI: https://doi.org/10.1007/s00216-018-0863-7

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