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

Autor: Yimu Zhao, Amandine Godier-Furnemont, Noortje A.M. Bax, Carlijn V.C. Bouten, Lewis M. Brown, Barry Fine, Gordana Vunjak-Novakovic
Přispěvatelé: Cell-Matrix Interact. Cardiov. Tissue Reg., Soft Tissue Biomech. & Tissue Eng., Center for Care & Cure Technology Eindhoven, NeuroPlatform, ICMS Core
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Molecular and Cellular Cardiology, 166, 137-151. Academic Press Inc.
J Mol Cell Cardiol
ISSN: 0022-2828
DOI: 10.1016/j.yjmcc.2022.02.003
Popis: 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.
Databáze: OpenAIRE
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