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Infarct in the Heart: What's MMP-9 Got to Do with It?
Mediha Becirovic-Agic1,2, Upendra Chalise1,2, Michael J Daseke1,2,3
1Center for Heart and Vascular Research, Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68102, USA.
Insights
Matrix metalloproteinase 9 (MMP-9) plays a complex role in heart attack wound healing. Targeting only its harmful effects, not all actions, is key for future therapies.
Area of Science:
- Cardiovascular biology
- Wound healing research
- Biochemistry
Background:
- Matrix metalloproteinase 9 (MMP-9) is linked to myocardial infarction (MI) mortality and cardiac dysfunction.
- Clinical trials of MMP-9 inhibitors have yielded disappointing results.
Purpose of the Study:
- To review the multifaceted roles of MMP-9 in myocardial infarction (MI) wound healing.
- To emphasize the need for targeted inhibition of MMP-9's detrimental actions.
Main Methods:
- Literature review of studies on MMP-9 in cardiac repair.
- Analysis of MMP-9 secretion by various cardiac cells.
- Examination of MMP-9's effects on inflammation, neovascularization, and scar formation.
Main Results:
- MMP-9 is secreted by leukocytes, cardiomyocytes, fibroblasts, and endothelial cells during cardiac repair.
- MMP-9 modulates inflammation, promoting resolution and cell transition.
- MMP-9 influences neovascularization and scar stiffness.
Conclusions:
- MMP-9 has a dual role in cardiac wound healing, with both beneficial and detrimental effects.
- Targeting MMP-9 requires a nuanced approach, focusing solely on its harmful actions.
- Understanding downstream signaling pathways of MMP-9 is crucial for developing effective therapies.
Abstract:
Over the past three decades, numerous studies have shown a strong connection between matrix metalloproteinase 9 (MMP-9) levels and myocardial infarction (MI) mortality and left ventricle remodeling and dysfunction. Despite this fact, clinical trials using MMP-9 inhibitors have been disappointing. This review focuses on the roles of MMP-9 in MI wound healing. Infiltrating leukocytes, cardiomyocytes, fibroblasts, and endothelial cells secrete MMP-9 during all phases of cardiac repair. MMP-9 both exacerbates the inflammatory response and aids in inflammation resolution by stimulating the pro-inflammatory to reparative cell transition. In addition, MMP-9 has a dual effect on neovascularization and prevents an overly stiff scar. Here, we review the complex role of MMP-9 in cardiac wound healing, and highlight the importance of targeting MMP-9 only for its detrimental actions. Therefore, delineating signaling pathways downstream of MMP-9 is critical.
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