Matrix Metalloproteinases: Drug Targets for Myocardial Infarction

Yabluchanskiy, Andriy; Li, Yaojun; Chilton, Robert; Lindsey, Merry L.

doi:10.2174/138945013804999007

Cited by 11 publications

(9 citation statements)

References 96 publications

(113 reference statements)

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“…MMP8 inhibition has been proposed as a potential therapeutic target for several diseases, including sepsis (8, 19, 21), inflammatory bowel disease (22), chronic obstructive pulmonary disease (23), cerebral ischemia (18), acute myocardial infarction (24), and acute lung injury (25). Success depends on target specificity of the compound.…”

Section: Discussionmentioning

confidence: 99%

Role of matrix metalloproteinase‐8 as a mediator of injury in intestinal ischemia and reperfusion

et al. 2016

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Acute mesenteric ischemia is associated with high morbidity and mortality. In recent studies, we found that the intestine is an important source of matrix metalloproteinase (MMP)8 during intestinal injury. We hypothesized that genetic ablation or pharmacological inhibition of MMP8 would reduce intestinal injury in mice subjected to intestinal ischemia-reperfusion (I/R) injury. Male mice aged 8-12 wk were subjected to intestinal I/R injury by transient occlusion of the superior mesenteric artery for 30 min. MMP8 was inhibited by genetic and pharmacological approaches. In vivo study endpoints included several functional, histological, and biochemical assays. Intestinal sections were assessed for barrier function and expression of tight junction proteins. I/R injury led to increased intestinal and systemic expression of MMP8. This increase was associated with increased intestinal neutrophil infiltration, epithelial injury, and permeability. I/R injury was associated with increased systemic inflammation and weight loss. These parameters were ameliorated by inhibiting MMP8. I/R injury caused a loss of the tight junction protein claudin-3, which was ameliorated by genetic ablation of MMP8. MMP8 plays an important role in intestinal I/R injury through mechanisms involving increased inflammation and loss of claudin-3. Inhibition of MMP8 is a potential therapeutic strategy in this setting.-Daly, M. C., Atkinson, S. J., Varisco, B. M., Klingbeil L., Hake, P., Lahni, P., Piraino, G., Wu, D., Hogan, S. P., Zingarelli, B., Wong, H. R. Role of matrix metalloproteinase-8 as a mediator of injury in intestinal ischemia and reperfusion.

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Section: Discussionmentioning

confidence: 99%

Role of matrix metalloproteinase‐8 as a mediator of injury in intestinal ischemia and reperfusion

et al. 2016

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“…Neutrophil-derived MMP-9 exerts early effects in the MI setting by degrading ECM and facilitating macrophage cell infiltration into the infarct area (19,36). Macrophages are another rich source of MMP-9.…”

Section: Mmp-9 Expression In Post-mi Leukocytesmentioning

confidence: 99%

“…Proinflammatory M1 macrophages dominate at day 1 post-MI, whereas anti-inflammatory M2 macrophages dominate starting from day 3 (37). M1 macrophages contribute MMP-9 and stimulate ECM degradation, whereas M2 macrophages contribute growth factors that regulate fibroblast differentiation and stimulate ECM production and deposition to form the infarct scar (36). The transition toward an M1 or M2 state is based on the local tissue environment (38).…”

Section: Mmp-9 Expression In Post-mi Leukocytesmentioning

confidence: 99%

“…Thrombolytic agents and anticoagulants are essential for early management of patients with acute MI; however, their use as well as medications such as converting enzyme (ACE) inhibitors, aldosterone antagonists, beta blockers, and statins, increase MMP-9 plasma concentrations in patients with acute MI (46,47). At the same time, most of these medications directly or indirectly inhibit MMP-9 activity and expression (36,48).…”

Section: Mmp-9 As a Therapeutic Targetmentioning

confidence: 99%

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

et al. 2015

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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. 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.

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“…Matrix metalloproteinases (MMPs) are enzymes that play a key role in cardiac remodeling and the development of adverse consequences after MI [11,12]. Peterson and colleagues [13] reported that MMP inhibition attenuates LV remodeling and dysfunction in a rat model of progressive heart failure.…”

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confidence: 99%

Left Ventricular Unloading After Acute Myocardial Infarction Reduces MMP/JNK Associated Apoptosis and Promotes FAK Cell-Survival Signaling

Wei

Evans

et al. 2016

The Annals of Thoracic Surgery

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Matrix Metalloproteinases: Drug Targets for Myocardial Infarction

Cited by 11 publications

References 96 publications

Role of matrix metalloproteinase‐8 as a mediator of injury in intestinal ischemia and reperfusion

Role of matrix metalloproteinase‐8 as a mediator of injury in intestinal ischemia and reperfusion

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

Left Ventricular Unloading After Acute Myocardial Infarction Reduces MMP/JNK Associated Apoptosis and Promotes FAK Cell-Survival Signaling

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