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Artif Organs. 2019 Sep 8. doi: 10.1111/aor.13566. [Epub ahead of print]

Impact of Left Ventricular Assist Device Therapy on the Cardiac Proteome and Metabolome Composition in Ischemic Cardiomyopathy.

Author information

1
Department of Cardiovascular Surgery, University Heart Center Freiburg • Bad Krozingen, Freiburg, Germany.
2
Faculty of Medicine, University of Freiburg, Freiburg, Germany.
3
Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, Freiburg, Germany.
4
Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany.
5
Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany.
6
Faculty of Biology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
7
Institute for Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany.
8
Center for Biological Systems Analysis ZBSA, Albert-Ludwigs-University, Freiburg, 79104, Germany.
9
BIOSS Center for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
10
Institute of Surgical Pathology, Medical Center, University of Freiburg, Freiburg, Germany.
11
German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

BACKGROUND:

The changes in the myocardial proteome and metabolome associated with left ventricular assist device (LVAD) therapy in patients with ischemic cardiomyopathy (ICM) are poorly characterized. We investigated the impact of mechanical unloading following LVAD therapy on the myocardial proteome and metabolome.

METHODS:

Matched samples of 5 patients' myocardial tissue, harvested at time of LVAD implant ("pre-LVAD") or heart transplant ("post-LVAD") were studied by quantitative proteomics and metabolomics as well as being probed for T-tubule structure and connexin-43 distribution. Moreover, pre-LVAD proteome profiles of ICM context were bioinformatically compared to pre-LVAD proteome profiles of dilate cardiac myopathy (DCM).

RESULTS:

More than 2120 proteins were reliably identified and quantified in paired patient samples. LVAD therapy led to proteomic remodelling, including reduced levels of α-1-antichymotrypsin together with an overall decrease of immune response proteins and an increase of proteins involved in membrane biology. Metabolomics highlighted increased glucose and glucose-6-phosphate levels in the left ventricle upon LVAD therapy. Wheat germ agglutinin staining demonstrated improved T-tubule structure. Connexin-43 displayed a trend for more pronounced intercalated disc localization. In comparing pre-LVAD proteome profiles of ICM context with pre-LVAD proteome profiles of dilate cardiac myopathy (DCM) we noticed an overrepresentation in ICM of proteins accosiated with humoral immune response.

CONCLUSIONS:

Our findings underline an impact of LVAD therapy on left ventricular biology in ICM. The proteomic, metabolomic, and structural alterations described here are typically associated with cardiac recovery. On the molecular level, our findings indicate the possibility of cardiac remodeling under LVAD therapy in ICM. This article is protected by copyright. All rights reserved.

KEYWORDS:

left ventricular assist device; mechanical unloading; reverse remodelling

PMID:
31494943
DOI:
10.1111/aor.13566

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