Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts.

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Stem Cell Biology

Background:

• Pathophysiological conditions like myocardial infarction cause cardiac fibrosis, leading to stiffened heart tissue.
• Understanding cardiomyocyte interaction with fibrotic matrix is crucial for cardiac cell therapy and disease mechanisms.

Purpose of the Study:

• To engineer an in vitro model of cardiac fibrotic tissue using hydrogels.
• To investigate cardiomyocyte behavior and gene expression in response to matrix rigidity.

Main Methods:

• Generated induced pluripotent stem cell-derived cardiomyocytes.
• Cultured cardiomyocytes on polyacrylamide hydrogels mimicking healthy and fibrotic cardiac tissue elasticity.
• Performed transcriptional profiling to analyze gene expression changes.

Main Results:

• Cardiomyocytes on fibrotic-like matrices showed significant upregulation of fibrosis-associated transcripts (collagen I/III, decorin, lumican, periostin).
• Matrix metalloproteinases, their inhibitors, and insulin-like growth factor 2 were also elevated.
• Primary cardiac fibroblasts did not exhibit comparable responses.

Conclusions:

• Matrix stiffening actively alters cardiomyocyte gene expression, providing a transcriptomic fingerprint of pathological conditions.
• Presents a novel, reproducible hydrogel-based model for studying cell-matrix interactions in fibrotic environments.
• Findings highlight the role of matrix stiffening in cardiomyocyte function and heart failure progression.