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Analytical and Bioanalytical Chemistry

, Volume 410, Issue 7, pp 1965–1976 | Cite as

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

  • Ganesh V. Halade
  • Anela Dorbane
  • Kevin A. Ingle
  • Vasundhara Kain
  • Jean-Marie Schmitter
  • Boutayna Rhourri-Frih
Research Paper

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.

Keywords

Myocardial infarction Lipids Ischemic myocardium Resolution of inflammation Bioactive lipid molecules 

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

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_863_MOESM1_ESM.pdf (708 kb)
ESM 1 (PDF 707 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ganesh V. Halade
    • 1
  • Anela Dorbane
    • 2
  • Kevin A. Ingle
    • 1
  • Vasundhara Kain
    • 1
  • Jean-Marie Schmitter
    • 2
  • Boutayna Rhourri-Frih
    • 2
  1. 1.Division of Cardiovascular Disease, Department of MedicineThe University of Alabama at BirminghamBirminghamUSA
  2. 2.Chimie et Biologie des Membranes et NanoobjetsUniversity of BordeauxBordeauxFrance

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