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Matrix metalloproteinase-9: Many shades of function in cardiovascular disease
Andriy Yabluchanskiy1, Yonggang Ma, Rugmani Padmanabhan Iyer
11San Antonio Cardiovascular Proteomics Center, San Antonio, Texas;
Abstract:
Matrix metalloproteinase (MMP)-9, one of the most widely investigated MMPs, regulates pathological remodeling processes that involve inflammation and fibrosis in cardiovascular disease. MMP-9 directly degrades extracellular matrix (ECM) proteins and activates cytokines and chemokines to regulate tissue remodeling. MMP-9 deletion or inhibition has proven overall beneficial in multiple animal models of cardiovascular disease. As such, MMP-9 expression and activity is a common end point measured. MMP-9 cell-specific overexpression, however, has also proven beneficial and highlights the fact that little information is available on the underlying mechanisms of MMP-9 function. In this review, we summarize our current understanding of MMP-9 physiology, including structure, regulation, activation, and downstream effects of increased MMP-9. We discuss MMP-9 roles during inflammation and fibrosis in cardiovascular disease. By concentrating on the substrates of MMP-9 and their roles in cardiovascular disease, we explore the overall function and discuss future directions on the translational potential of MMP-9 based therapies.
Insights
Matrix metalloproteinase-9 (MMP-9) plays a key role in cardiovascular disease by remodeling tissues. Understanding MMP-9
Area of Science:
- Cardiovascular Biology
- Enzymology
- Molecular Medicine
Background:
- Matrix metalloproteinase-9 (MMP-9) is a key enzyme implicated in cardiovascular disease pathogenesis.
- MMP-9 regulates extracellular matrix (ECM) degradation and modulates inflammatory responses.
- While MMP-9 inhibition is often beneficial, cell-specific overexpression also shows therapeutic potential, indicating complex roles.
Purpose of the Study:
- To review the current understanding of MMP-9 physiology, including its structure, regulation, and activation.
- To elucidate the specific roles of MMP-9 in inflammation and fibrosis within cardiovascular disease.
- To explore the substrates of MMP-9 and their impact on cardiovascular pathologies.
Main Methods:
- Literature review synthesizing existing research on MMP-9.
- Analysis of MMP-9's structure, regulation, and activation mechanisms.
- Examination of MMP-9's downstream effects and substrate interactions in cardiovascular disease models.
Main Results:
- MMP-9 directly degrades ECM proteins and influences cytokine/chemokine activity.
- MMP-9 deletion/inhibition shows benefits in animal models of cardiovascular disease.
- The precise mechanisms and context-dependent functions of MMP-9 require further investigation.
Conclusions:
- MMP-9 is a critical regulator of pathological remodeling in cardiovascular disease.
- Further research into MMP-9 substrates and cell-specific functions is needed.
- MMP-9-targeted therapies hold translational potential for cardiovascular conditions.
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