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

Abstract

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. While 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. While we use myocardial infarction as the example process, similar events occur in other inflammatory and wound healing conditions.

Retracted: IRAK3 gene silencing prevents cardiac rupture and ventricular remodeling through negative regulation of the NF‐κB signaling pathway in a mouse model of acute myocardial infarction

“…In the PPI network, IRAK3 and MMP‐9 were found to have interaction with more DEGs, and these two genes also interacted with each other, suggesting that IRAK3 and MMP‐9 might play important roles in MI‐related diseases. Indeed, many studies have shown that MMP‐9 is associated with MI (Deleon‐Pennell, Altara, Yabluchanskiy, Modesti, & Lindsey, ; Iyer, Jung, & Lindsey, ), but there are few studies demonstrating the effects of IRAK3 on MI or the underlying molecular mechanisms. Therefore, the focus of the experiment shifted to the effect IRAK3 had on MI, along with the possible molecular mechanisms.…”

Systemic inflammation on postnatal days 21 and 28 and indicators of brain dysfunction 2years later among children born before the 28th week of gestation

“…[44–46] These pleotropic properties also indicate that MMP-9, along with the tissue inhibitor of metalloproteinase-1, which helps regulate the activity of MMP-9, operate in complex ways, only some of which are probably related to inflammation. Indeed, the authors of one review wrote, “we still do not fully understand the complexity of MMP-9 mechanisms of action.”[47] In light of these limitations, we are unable to explain why we found that elevated concentrations of MMP-9 were associated with reduced risk of ventriculomegaly.…”

4‐Hydroxycinnamic acid suppresses airway inflammation and mucus hypersecretion in allergic asthma induced by ovalbumin challenge

“…In asthma pathogenesis, overproduction of NO synthesized by iNOS leads to an imbalance of Th2 cells, which results in acceleration of the asthmatic response, including inflammatory cell infiltration, airway constriction, and a tissue remodeling process (Comer et al, ; Deacon & Knox, ). The level of the COX‐2 protein is elevated by stimulation of toxic materials such as lipopolysaccharide, chemicals, and allergens; COX‐2 is regarded as a crucial protein in the progression of asthma (Deleon‐Pennell, Altara, Yabluchanskiy, Modesti, & Lindsey, ; Rumzhum & Ammit, ). An increased in COX‐2 levels induces elevation of the level of prostaglandins, which aggravates the inflammatory response (Siloşi et al, ).…”

“…The level of the COX-2 protein is elevated by stimulation of toxic materials such as lipopolysaccharide, chemicals, and allergens; COX-2 is regarded as a crucial protein in the progression of asthma (Deleon-Pennell, Altara, Yabluchanskiy, Modesti, & Lindsey, 2015;Rumzhum & Ammit, 2016). An increased in COX-2 levels induces elevation of the level of prostaglandins, which aggravates the inflammatory response (Siloşi et al, 2014).…”