Enzymatic extracellular matrix remodeling in ex vivo slices of aged myocardium
- 1National University of Singapore
Abstract
Cardiac aging is accompanied by extracellular matrix (ECM) remodeling and increased myocardial stiffness, which may contribute to age-associated functional decline. However, whether direct remodeling of the aged cardiac ECM can modify myocardial mechanics and function remains poorly understood. Here, we established an ex vivo living myocardial slice platform to investigate whether enzymatic remodeling of the aged ECM can alter myocardial structure, mechanics, and function. Left ventricular myocardial slices (LMS) from young and aged mice were maintained under static stretch for 48 hours using a custom 3D-printed culture setup. Aged slices were treated with collagenase and subsequently characterized using quantitative imaging, tensile testing, contractility measurements, and transcriptomic analysis. Aged myocardium exhibited increased collagen and fibronectin abundance, altered collagen network architecture, and increased stiffness compared with young tissue. Collagenase treatment reduced collagen and network complexity and reduced myocardial stiffness toward young tissue values without compromising ultimate tensile stress. Despite these structural and biomechanical changes, age-associated differences in myocardial contractility remained comparable across groups. Transcriptomic analysis indicated that treated aged tissue largely retained its age-associated molecular phenotype, despite pathway-level shifts involving metabolism, cardiac function, and inflammatory responses. These findings demonstrate that enzymatic ECM remodeling can modify the aged myocardial mechanical environment while selected functional and transcriptional features of aging persist over 48 hours. The LMS platform provides a controllable ex vivo tissue-level approach for investigating ECM contributions during cardiac aging and evaluating strategies for ECM engineering.
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BibTeX
@misc{hengst2026enzymatic,
title = {{Enzymatic extracellular matrix remodeling in ex vivo slices of aged myocardium}},
author = {R. M. Hengst and E. M. Spaans and M. F. H. Ramli and A. R. Sun and V. J. Y. Lai and K. W. Leong and Y. Zhu and R. S. Foo and J. Zhu and C. J. Chan and L. H. Liang and J. L. Young},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.760075},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.760075v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Enzymatic extracellular matrix remodeling in ex vivo slices of aged myocardium
AU - R. M. Hengst
AU - E. M. Spaans
AU - M. F. H. Ramli
AU - A. R. Sun
AU - V. J. Y. Lai
AU - K. W. Leong
AU - Y. Zhu
AU - R. S. Foo
AU - J. Zhu
AU - C. J. Chan
AU - L. H. Liang
AU - J. L. Young
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.760075
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.760075v1
AB - Cardiac aging is accompanied by extracellular matrix (ECM) remodeling and increased myocardial stiffness, which may contribute to age-associated functional decline. However, whether direct remodeling of the aged cardiac ECM can modify myocardial mechanics and function remains poorly understood. Here, we established an ex vivo living myocardial slice platform to investigate whether enzymatic remodeling of the aged ECM can alter myocardial structure, mechanics, and function. Left ventricular myocardial slices (LMS) from young and aged mice were maintained under static stretch for 48 hours using a custom 3D-printed culture setup. Aged slices were treated with collagenase and subsequently characterized using quantitative imaging, tensile testing, contractility measurements, and transcriptomic analysis. Aged myocardium exhibited increased collagen and fibronectin abundance, altered collagen network architecture, and increased stiffness compared with young tissue. Collagenase treatment reduced collagen and network complexity and reduced myocardial stiffness toward young tissue values without compromising ultimate tensile stress. Despite these structural and biomechanical changes, age-associated differences in myocardial contractility remained comparable across groups. Transcriptomic analysis indicated that treated aged tissue largely retained its age-associated molecular phenotype, despite pathway-level shifts involving metabolism, cardiac function, and inflammatory responses. These findings demonstrate that enzymatic ECM remodeling can modify the aged myocardial mechanical environment while selected functional and transcriptional features of aging persist over 48 hours. The LMS platform provides a controllable ex vivo tissue-level approach for investigating ECM contributions during cardiac aging and evaluating strategies for ECM engineering.
ER -