Relaxin induces mast cell inhibition and reduces ventricular arrhythmias in a swine model of acute myocardial infarction

Nistri, Silvia; Cinci, Lorenzo; Perna, A. M.; Masini, Emanuela; Mastroianni, Rosanna; Bani, Danièle

doi:10.1016/j.phrs.2007.11.001

Cited by 48 publications

(48 citation statements)

References 33 publications

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“…Moreover, RLX was able to counteract the adverse bronchial remodeling induced by CS exposure by reducing goblet cell hyperplasia, smooth muscle wall thickening, and fibrosis, and it was able to blunt emphysema of the distal air spaces. These effects of RLX fit well with previous reports that this hormone reduces inflammation and fibrosis in many in vitro and in vivo models of disease (Masini et al, 1994(Masini et al, , 2004Nistri et al, 2003Nistri et al, , 2008Lekgabe et al, 2005;Bonacchi et al, 2009;Sasser, 2013;Royce et al, 2014;Samuel et al, 2014). In Fig.…”

Section: Discussionsupporting

confidence: 91%

Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin)

Pini

Boccalini

Lucarini

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD), which is characterized by airway remodeling, lung inflammation and fibrosis, emphysema, and respiratory failure. The current therapies can improve COPD management but cannot arrest its progression and reduce mortality. Hence, there is a major interest in identifying molecules susceptible of development into new drugs to prevent or reduce CS-induced lung injury. Serelaxin (RLX), or recombinant human relaxin-2, is a promising candidate because of its anti-inflammatory and antifibrotic properties highlighted in lung disease models. Here, we used a guinea pig model of CSinduced lung inflammation, and remodeling reproducing some of the hallmarks of COPD. Animals exposed chronically to CS (8 weeks) were treated with vehicle or RLX, delivered by osmotic pumps (1 or 10 mg/day) or aerosol (10 mg/ml/day) during CS treatment. Controls were nonsmoking animals. RLX maintained airway compliance to a control-like pattern, likely because of its capability to counteract lung inflammation and bronchial remodeling. In fact, treatment of CS-exposed animals with RLX reduced the inflammatory recruitment of leukocytes, accompanied by a significant reduction of the release of proinflammatory cytokines (tumor necrosis factor a and interleukin-1b). Moreover, RLX was able to counteract the adverse bronchial remodeling and emphysema induced by CS exposure by reducing goblet cell hyperplasia, smooth muscle thickening, and fibrosis. Of note, RLX delivered by aerosol has shown a comparable efficacy to systemic administration in reducing CS-induced lung dysfunction and damage. In conclusion, RLX emerges as a new molecule to counteract CS-induced inflammatory lung diseases.

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Section: Discussionsupporting

confidence: 91%

Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin)

Pini

Boccalini

Lucarini

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…Relaxin has been administered intravenously at the time of reperfusion in a porcine ischemia-reperfusion model. 82 In this study the administration of relaxin led to decreases in myonecrosis, cardiac myocyte apoptosis, and leukocyte infiltration into the injured myocardium. 82 These results have led to porcine studies in which control or human relaxin overexpressing C2C12 myoblasts were transplanted into a model of chronic ischemia.…”

Section: Mediators Of Extracellular Matrixmentioning

confidence: 65%

“…82 In this study the administration of relaxin led to decreases in myonecrosis, cardiac myocyte apoptosis, and leukocyte infiltration into the injured myocardium. 82 These results have led to porcine studies in which control or human relaxin overexpressing C2C12 myoblasts were transplanted into a model of chronic ischemia. 76 The chronic expression of relaxin led to the increased local expression of MMP-2 and VEGF.…”

Section: Mediators Of Extracellular Matrixmentioning

confidence: 65%

Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy

Penn¹,

Mangi

2008

Circulation Research

134

103

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Abstract-Cell-based therapies for the prevention and treatment of cardiac dysfunction offer the potential to significantly modulate cardiac function and improve outcomes in patients with cardiovascular disease. To date several clinical studies have suggested the potential efficacy of several different stem cell types; however, the benefits seen in clinical trials have been inconsistent and modest. In parallel, preclinical studies have identified key events in the process of cell-based myocardial repair, including stem cell homing, engraftment, survival, paracrine factor release, and differentiation that need to be optimized to maximize cardiac repair and function. The inconsistent and modest benefits seen in clinical trials combined with the preclinical identification of mediators responsible for key events in cell-based cardiac repair offers the potential for cell-based therapy to advance to cell-based gene therapy in an attempt to optimize these key events in the hope of maximizing clinical benefit. Below we discuss potential key events in cardiac repair and the mediators of these events that could be of potential interest for genetic enhancement of stem cell-based cardiac repair. (Circ Res.

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“…In the setting of acute ischemic arrest, relaxin was able to significantly reduce the adverse outcomes of asystole, ventricular tachyarrhythmias, or bradycardiac arrests, possibly through anti-inflammatory effects by inhibiting mast cell activation. 41 Further research is needed to weigh the role of immune, inflammatory, or hormonal modulation of PEA pathways, especially in the context of underlying comorbidities such as diabetes mellitus, heart failure, and other proinflammatory disease states. An intriguing hypothesis, based on the possibility that β-blockers protect against the expression of VT/VF during ischemia, is that inflammatory signals may allow PEA to emerge by default.…”

Section: Cellular Mechanisms and Contractile Dysfunctionmentioning

confidence: 99%