SSR69071, an elastase inhibitor, reduces myocardial infarct size following ischemia–reperfusion injury

Bidouard, Jean‐Pierre; Duval, Nicole; Kapui, Zoltán; Herbert, Jean‐Marc; O'Connor, Stephen E.; Janiak, Philip

doi:10.1016/s0014-2999(03)01298-6

Cited by 24 publications

(16 citation statements)

References 12 publications

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“…Experiments in a number of cardiac disease models have demonstrated that the protection of the myocardial elastic fibers against elastase-driven degradation was associated with better recovery. For example, treatment with a neutrophil elastase inhibitor before reperfusion post-MI inhibited the proteolytic destruction of elastic fibers in the heart and reduced infarct size in rodent (34) and rabbit models (35). Additionally, a transgenic mouse model overexpressing a selective serine elastase inhibitor Figure 6.…”

Section: Discussionmentioning

confidence: 99%

The Antidiabetic Hormone Glucagon-Like Peptide-1 Induces Formation of New Elastic Fibers in Human Cardiac Fibroblasts After Cross-Activation of IGF-IR

Qa'aty

Wang

et al. 2015

Endocrinology

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Glucagon-like peptide 1 (GLP-1) is a metabolic hormone involved in the stimulation of insulin biosynthesis and secretion. It has been recently reported that GLP-1 also exerts cardioprotective effects and facilitates functional recovery after myocardial infarction through GLP-1 receptor-mediated signaling in cardiomyocytes. GLP-1 treatment has been also demonstrated to produce sustained improvement in cardiac function in long-term studies, suggesting the involvement of mechanisms beyond the acute metabolic and cytoprotective effects. For example, the possible interaction of GLP-1 with the cardiac fibroblasts, which are responsible for the postinfarct remodeling and extracellular matrix production, has not been previously explored. Here, we report that cultures of human cardiac fibroblasts treated with GLP-1 peptides display a selective up-regulation in elastin gene expression and a consequent increase in elastic fibers production, in the absence of the classic GLP-1 receptor. Importantly, we provide experimental evidence that this GLP-1-induced elastogenesis is triggered through the cross-activation of the IGF-I receptor. Because GLP-1 does not stimulate deposition of collagen I, nor promote the proliferation or apoptosis of cultured cardiac fibroblasts, we speculate that its elastogenic effect may also contribute to the beneficial remodeling of the human heart after myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

The Antidiabetic Hormone Glucagon-Like Peptide-1 Induces Formation of New Elastic Fibers in Human Cardiac Fibroblasts After Cross-Activation of IGF-IR

Qa'aty

Wang

et al. 2015

Endocrinology

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“…NE can cleave and activate pro-MMP-9, indicating an interactive action of PMN-derived molecules [51]. NE is released in the early stages of ischemia, and inhibition of NE has been shown to reduce infarct size [52]. Similarly, a selective NE inhibitor protects against myocardial stunning after ischemia/reperfusion in swine [53].…”

Section: Reviewmentioning

confidence: 99%

Neutrophil roles in left ventricular remodeling following myocardial infarction

Yabluchanskiy

Lindsey

2013

Fibrogenesis Tissue Repair

153

121

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Polymorphonuclear granulocytes (PMNs; neutrophils) serve as key effector cells in the innate immune system and provide the first line of defense against invading microorganisms. In addition to producing inflammatory cytokines and chemokines and undergoing a respiratory burst that stimulates the release of reactive oxygen species, PMNs also degranulate to release components that kill pathogens. Recently, neutrophil extracellular traps have been shown to be an alternative way to trap microorganisms and contain infection. PMN-derived granule components are also involved in multiple non-infectious inflammatory processes, including the response to myocardial infarction (MI). In this review, we will discuss the biological characteristics, recruitment, activation, and removal of PMNs, as well as the roles of PMN-derived granule proteins in inflammation and innate immunity, focusing on the MI setting when applicable. We also discuss future perspectives that will direct research in PMN biology.

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“…[1][2][3][4][5] This cycle of cell recruitment is often self-amplified and sustained in MI/R and leads to further cell necrosis, scar formation, and cardiac dysfunction. [6][7][8][9][10][11] Adenine nucleotides such as ATP and AMP are potent danger-associated molecular patterns that trigger chemotactic migration, vessel wall adhesion, and proinflammatory cytokine production by early infiltrating leukocytes such as neutrophils and macrophages. [12][13][14][15] However, these adenine nucleotides can be dephosphorylated to adenosine.…”

mentioning

confidence: 99%

Adenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury

Shin

Wang

Zemskova

et al. 2018

JAHA

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BackgroundDuring myocardial ischemia/reperfusion (MI/R) injury, there is extensive release of immunogenic metabolites that activate cells of the innate immune system. These include ATP and AMP, which upregulate chemotaxis, migration, and effector function of early infiltrating inflammatory cells. These cells subsequently drive further tissue devitalization. Mesenchymal stromal cells (MSCs) are a potential treatment modality for MI/R because of their powerful anti‐inflammatory capabilities; however, the manner in which they regulate the acute inflammatory milieu requires further elucidation. CD73, an ecto‐5′‐nucleotidase, may be critical in regulating inflammation by converting pro‐inflammatory AMP to anti‐inflammatory adenosine. We hypothesized that MSC‐mediated conversion of AMP into adenosine reduces inflammation in early MI/R, favoring a micro‐environment that attenuates excessive innate immune cell activation and facilitates earlier cardiac recovery.Methods and ResultsAdult rats were subjected to 30 minutes of MI/R injury. MSCs were encapsulated within a hydrogel vehicle and implanted onto the myocardium. A subset of MSCs were pretreated with the CD73 inhibitor, α,β‐methylene adenosine diphosphate, before implantation. Using liquid chromatography/mass spectrometry, we found that MSCs increase myocardial adenosine availability following injury via CD73 activity. MSCs also reduce innate immune cell infiltration as measured by flow cytometry, and hydrogen peroxide formation as measured by Amplex Red assay. These effects were dependent on MSC‐mediated CD73 activity. Finally, through echocardiography we found that CD73 activity on MSCs was critical to optimal protection of cardiac function following MI/R injury.Conclusions MSC‐mediated conversion of AMP to adenosine by CD73 exerts a powerful anti‐inflammatory effect critical for cardiac recovery following MI/R injury.

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SSR69071, an elastase inhibitor, reduces myocardial infarct size following ischemia–reperfusion injury

Cited by 24 publications

References 12 publications

The Antidiabetic Hormone Glucagon-Like Peptide-1 Induces Formation of New Elastic Fibers in Human Cardiac Fibroblasts After Cross-Activation of IGF-IR

The Antidiabetic Hormone Glucagon-Like Peptide-1 Induces Formation of New Elastic Fibers in Human Cardiac Fibroblasts After Cross-Activation of IGF-IR

Neutrophil roles in left ventricular remodeling following myocardial infarction

Adenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury

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