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 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.
Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, MS, USA.
Kristine Y
KY
Deleon-Pennell
Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, MS, USA.
Raffaele
R
Altara
Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, MS, USA.
Andriy
A
Yabluchanskiy
Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Università degli Studi di Firenze, Firenze, Italy.
Alessandra
A
Modesti
Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, MS, USA.|Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS, USA.
Merry L
http://orcid.org/0000-0002-4090-0391
ML
Lindsey
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020257:Ventricular Remodeling / Q000235:genetics*; D014945:Wound Healing
D018925:Chemokines; D016207:Cytokines; D020780:Matrix Metalloproteinase 9
MMP; chemokines; cytokines; inflammation; myocardial infarction; proteomics