The circular relationship between matrix metalloproteinase‐9 and inflammation following myocardial infarction

Matrix metalloproteinase‐9 (MMP‐9) regulates remodeling of the left ventricle after myocardial infarction (MI) and is tightly linked to the inflammatory response. The inflammatory response serves to recruit leukocytes as part of the wound healing reaction to the MI injury, and infiltrated leukocytes...

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Published in:IUBMB life 2015-08, Vol.67 (8), p.611-618
Main Authors: Deleon‐Pennell, Kristine Y., Altara, Raffaele, Yabluchanskiy, Andriy, Modesti, Alessandra, Lindsey, Merry L.
Format: Article
Language:English
Subjects:
Animals
chemokines
Chemokines - metabolism
cytokines
Cytokines - metabolism
Humans
inflammation
Inflammation - genetics
Inflammation - metabolism
Inflammation - pathology
Leukocytes - metabolism
Matrix Metalloproteinase 9 - biosynthesis
Matrix Metalloproteinase 9 - genetics
Matrix Metalloproteinase 9 - metabolism
Mice
MMP
myocardial infarction
Myocardial Infarction - genetics
Myocardial Infarction - metabolism
Myocardial Infarction - pathology
proteomics
Ventricular Remodeling - genetics
Wound Healing
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Summary:Matrix metalloproteinase‐9 (MMP‐9) regulates remodeling of the left ventricle after myocardial infarction (MI) and is tightly linked to the inflammatory response. The inflammatory response serves to recruit leukocytes as part of the wound healing reaction to the MI injury, and infiltrated leukocytes produce cytokines and chemokines that stimulate MMP‐9 production and release. In turn, MMP‐9 proteolyzes cytokines and chemokines. Although in most cases, MMP‐9 cleavage of the cytokine or chemokine substrate serves to increase activity, there are cases where cleavage results in reduced activity. Global MMP‐9 deletion in mouse MI models has proven beneficial, suggesting inhibition of some aspects of MMP‐9 activity may be valuable for clinical use. At the same time, overexpression of MMP‐9 in macrophages has also proven beneficial, indicating that we still do not fully understand the complexity of MMP‐9 mechanisms of action. In this review, we summarize the cycle of MMP‐9 effects on cytokine production and cleavage to regulate leukocyte functions. Although we use MI as the example process, similar events occur in other inflammatory and wound healing conditions. © 2015 IUBMB Life, 67(8):611–618, 2015
ISSN:1521-6543
1521-6551
DOI:10.1002/iub.1408