MassIVE MSV000088676

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Changes in extracellular matrix in failing human non-ischemic and ischemic hearts with mechanical unloading

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Description

Ischemic and non-ischemic cardiomyopathies have distinct etiologies and underlying disease mechanisms, which require in-depth investigation for improved therapeutic interventions. The goal of this study was to use clinically obtained myocardium from healthy and heart failure patients, and characterize the changes in extracellular matrix (ECM) in ischemic and non-ischemic failing hearts, with and without mechanical unloading. Using tissue engineering methodologies, we also investigated how diseased human ECM, in the absence of systemic factors, can influence cardiomyocyte function. Heart tissues from heart failure patients with ischemic and non-ischemic cardiomyopathy were compared to explore differential disease phenotypes and reverse remodeling potential of left ventricular assisted device (LVAD) support at transcriptomic, proteomic and structural levels. The collected data demonstrated that the differential ECM compositions recapitulated the disease microenvironment and induced cardiomyocytes to undergo disease-like functional alterations. In addition, our study also revealed molecular profiles of non-ischemic and ischemic heart failure patients and explored the underlying mechanisms of etiology-specific impact on clinical outcome of LVAD support and tendency towards reverse remodeling. [doi:10.25345/C50G57] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Extracellular Matrix ; Heart Failure ; proteomics ; non-ischemic cardiomyopathy ; LVAD support ; ischemic cardiomyopathy ; disease niches ; traveling wave ion mobility spectrometry (TWIMS) ; Synapt G2 HDMS

Contact

Principal Investigators:
(in alphabetical order) 		Gordana Vunjak-Novakovic, Columbia University, United States
Lewis M. Brown, Columbia University, United States
Submitting User: proteomics2_columbia

Publications

Yimu Zhao, Amandine Godier-Furnemont, Noortje A.M. Bax, Carlijn VC Bouten, Lewis M. Brown, Barry Fine, Gordana Vunjak-Novakovic.
Changes in extracellular matrix in failing human non-ischemic and ischemic hearts with mechanical unloading.
J. Mol. Cell. Cardiol. 2022 (submitted).

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