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Updated: Mar 6, 2026
Author Spotlight: Studying Cardiac Cell-Matrix Interactions In Vitro
Published on: March 22, 2024
The impact of aging on cardiac extracellular matrix
Cesar A Meschiari1, Osasere Kelvin Ero1, Haihui Pan2
1Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Room G351-04, Jackson, MS, USA.
Insights
Cardiac aging involves cardiomyocyte hypertrophy and fibrosis, subtly impairing heart function. Matrix metalloproteinase-9 (MMP-9) plays a key role in these age-related cardiac changes and ECM remodeling.
Area of Science:
- Cardiovascular biology
- Aging research
- Molecular cardiology
Background:
- Cardiac aging is characterized by cellular, extracellular, and tissue-level changes.
- Hallmarks include cardiomyocyte hypertrophy, inflammation, and cardiac fibrosis.
- These changes subtly impair myocardial function, especially diastolic function.
Purpose of the Study:
- To review the roles of matrix metalloproteinases (MMPs), particularly MMP-9, in cardiac aging.
- To understand MMPs' influence on extracellular matrix (ECM) remodeling and cell signaling during aging.
- To explore the association between MMP-9, macrophages, and age-related cardiac dysfunction.
Main Methods:
- Review of existing literature on MMPs, ECM, and cardiac aging.
- Evaluation of MMP-9 expression and activity in the aging heart.
- Analysis of the interplay between MMPs, ECM components, and cellular signaling pathways.
Main Results:
- Cardiac aging involves increased collagen deposition and cross-linking, alongside enhanced ECM degradation capacity due to elevated MMPs.
- MMP-9 is significantly elevated in cardiac aging and contributes to ECM remodeling.
- MMP-9 modulates cell signaling by affecting cytokines, growth factors, and angiogenic factors.
- Macrophage numbers increase with age, correlating with elevated MMP-9 and regulating ECM/angiogenic responses.
Conclusions:
- Understanding MMP-ECM interactions in aging is crucial for comprehending cardiac dysfunction.
- Elevated MMP-9 and associated macrophage activity are key players in age-related cardiac remodeling.
- This knowledge may lead to novel diagnostic markers for early detection of age-related cardiac fibrosis and dysfunction.
Abstract:
Age-related changes in cardiac homeostasis can be observed at the cellular, extracellular, and tissue levels. Progressive cardiomyocyte hypertrophy, inflammation, and the gradual development of cardiac fibrosis are hallmarks of cardiac aging. In the absence of a secondary insult such as hypertension, these changes are subtle and result in slight to moderate impaired myocardial function, particularly diastolic function. While collagen deposition and cross-linking increase during aging, extracellular matrix (ECM) degradation capacity also increases due to increased expression of matrix metalloproteinases (MMPs). Of the MMPs elevated with cardiac aging, MMP-9 has been extensively evaluated and its roles are reviewed here. In addition to proteolytic activity on ECM components, MMPs oversee cell signaling during the aging process by modulating cytokine, chemokine, growth factor, hormone, and angiogenic factor expression and activity. In association with elevated MMP-9, macrophage numbers increase in an age-dependent manner to regulate the ECM and angiogenic responses. Understanding the complexity of the molecular interactions between MMPs and the ECM in the context of aging may provide novel diagnostic indicators for the early detection of age-related fibrosis and cardiac dysfunction.
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