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Updated: Oct 2, 2025

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

Yimu Zhao1, Amandine Godier-Furnemont1, Noortje A M Bax2

  • 1Department of Biomedical Engineering, Columbia University, New York 10032, USA.

Journal of Molecular and Cellular Cardiology
|February 27, 2022
PubMed

Insights

This study reveals how the extracellular matrix (ECM) in ischemic and non-ischemic cardiomyopathies affects heart cell function. Understanding these differences is key for developing targeted therapies for heart failure.

Area of Science:

  • Cardiovascular Biology
  • Biomaterials Science
  • Translational Medicine

Background:

  • Distinct etiologies of ischemic and non-ischemic cardiomyopathies necessitate targeted therapeutic strategies.
  • The extracellular matrix (ECM) plays a critical role in cardiac function and disease.
  • Understanding the interplay between ECM and cardiomyocytes is crucial for heart failure treatment.

Purpose of the Study:

  • To characterize extracellular matrix (ECM) changes in ischemic and non-ischemic cardiomyopathies.
  • To investigate the influence of diseased human ECM on cardiomyocyte function using tissue engineering.
  • To explore the differential disease phenotypes and reverse remodeling potential of mechanical unloading, such as left ventricular assist device (LVAD) support.

Main Methods:

  • Analysis of human myocardium from healthy, ischemic, and non-ischemic heart failure patients.
  • Application of tissue engineering methodologies to assess ECM-cardiomyocyte interactions.
  • Transcriptomic, proteomic, and structural analyses of heart tissues.
  • Evaluation of left ventricular assist device (LVAD) support effects.

Main Results:

  • Differential ECM compositions were identified in ischemic and non-ischemic failing hearts.
  • Diseased human ECM recapitulated disease microenvironments and induced cardiomyocyte dysfunction.
  • Molecular profiles distinguishing non-ischemic and ischemic heart failure were revealed.
  • Etiology-specific impacts on LVAD support outcomes and reverse remodeling were explored.

Conclusions:

  • Extracellular matrix (ECM) alterations are central to the distinct pathobiology of ischemic and non-ischemic cardiomyopathies.
  • Diseased ECM significantly influences cardiomyocyte function, independent of systemic factors.
  • Findings provide insights into etiology-specific responses to mechanical unloading and potential for reverse remodeling.

Keywords:
Disease nichesExtracellular matrixHeart failureIschemic cardiomyopathyLVAD supportNon-ischemic cardiomyopathyProteomics

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