Infarct in the heart: What’s MMP-9 got to do with it?

Mediha Becirovic-Agic; Upendra Chalise; Michael J. Daseke; Shelby Konfrst; Jeffrey D. Salomon; Paras K. Mishra; Merry L. Lindsey

doi:10.3390/biom11040491

Infarct in the heart: What’s MMP-9 got to do with it?

Mediha Becirovic-Agic, Upendra Chalise, Michael J. Daseke, Shelby Konfrst, Jeffrey D. Salomon, Paras K. Mishra, Merry L. Lindsey

Research output: Contribution to journal › Review article › peer-review

29 Scopus citations

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.

Original language	English (US)
Article number	491
Journal	Biomolecules
Volume	11
Issue number	4
DOIs	https://doi.org/10.3390/biom11040491
State	Published - Apr 2021

Keywords

Extracellular matrix
Inflammation
Macrophage
Matrix metalloproteinases
Neutrophil
Remodeling

ASJC Scopus subject areas

Biochemistry
Molecular Biology

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10.3390/biom11040491

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title = "Infarct in the heart: What{\textquoteright}s MMP-9 got to do with it?",

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.",

keywords = "Extracellular matrix, Inflammation, Macrophage, Matrix metalloproteinases, Neutrophil, Remodeling",

author = "Mediha Becirovic-Agic and Upendra Chalise and Daseke, {Michael J.} and Shelby Konfrst and Salomon, {Jeffrey D.} and Mishra, {Paras K.} and Lindsey, {Merry L.}",

note = "Funding Information: This research was funded by the National Institutes of Health under award numbers U54GM115458, HL129823, and HL137319, the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development under award number 5I01BX000505, and the Swedish Society for Medical Research under award number P19-0144. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies. All authors have reviewed and approved the article. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/biom11040491",

language = "English (US)",

volume = "11",

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T2 - What’s MMP-9 got to do with it?

AU - Becirovic-Agic, Mediha

AU - Chalise, Upendra

AU - Daseke, Michael J.

AU - Konfrst, Shelby

AU - Salomon, Jeffrey D.

AU - Mishra, Paras K.

AU - Lindsey, Merry L.

N1 - Funding Information: This research was funded by the National Institutes of Health under award numbers U54GM115458, HL129823, and HL137319, the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development under award number 5I01BX000505, and the Swedish Society for Medical Research under award number P19-0144. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies. All authors have reviewed and approved the article. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/4

Y1 - 2021/4

N2 - 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.

AB - 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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KW - Remodeling

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Infarct in the heart: What’s MMP-9 got to do with it?

Abstract

Keywords

ASJC Scopus subject areas

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