The Positive Inotropic Effect of Relaxin-2 in Human Atrial Myocardium is Preserved in End-Stage Heart Failure: Role of Gi-Phosphoinositide-3 Kinase Signaling

Dschietzig, Thomas; Alexiou, Konstantin; Kinkel, H.J.; Baumann, Gert; Matschke, Klaus; Stangl, Karl

doi:10.1016/j.cardfail.2010.08.011

Cited by 41 publications

(46 citation statements)

References 38 publications

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“…The H2 RLX protein (or RLX-1 in rodents) is the major circulating and stored form of RLX. In failing atria, the significant down-regulation of RXFP1, a receptor for RLX2 expression was observed compared with non-failing atria [65]. At first, it was considered that RLX exerts remarkable positive inotropy in atria but not in ventricles of rats, due to the lack of a relevant RXFP1 receptor on ventricular myocytes [65].…”

Section: Discussionmentioning

confidence: 99%

Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats

Lee

Choi

et al. 2016

Biomaterials

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In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM.

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Section: Discussionmentioning

confidence: 99%

Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats

Lee

Choi

et al. 2016

Biomaterials

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“…Relaxin gene expression was increased in HF patients with H1 > H2 in the LV and H2 > H1 in right atrium, suggesting that the atria may be a more important source of relaxin-2, which has also been proposed by others. 29,30 mRNA of preprorelaxin was doubled in the failing right atrium, but not in the LV. mRNA of prohormone convertase-1, a prorelaxin-processing enzyme, was also detected in atria, ventricles, coronary sinus, and antecubital veins.…”

Section: Expression In Heart Failurementioning

confidence: 93%

“…43 Extending these findings to humans, the effects of relaxin on cardiac tissue from controls and those with failing hearts was examined in 1 study. 30 Expression of the relaxin receptor, RXFP-1, was detectable in atrial but not in ventricular myocardium. Relaxin, assessed at half maximal effective concentration, increased maximum peak developed tension in atrial myocardium from both control and failing hearts.…”

Section: Atrial Inotropy/chronotropymentioning

confidence: 98%

Relaxin for the Treatment of Acute Decompensated Heart Failure

Goland

Elkayam

2016

Cardiology in Review

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Acute heart failure remains a major cause of morbidity, and its treatment requires an increasing investment of the health care system. Whereas success in treating chronic heart failure has been achieved over the last decades, several pharmacological approaches for acute heart failure have been introduced but have failed to demonstrate any clinical benefit. Serelaxin is a recombinant human relaxin-2 vasoactive peptide that causes systemic and renal vasodilation. Data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via neurohormonal, anti-inflammatory, antiremodeling, antifibrotic, anti-ischemic, and proangiogenic effects. Recently, a number of clinical trials have demonstrated that serelaxin infusion over 48 hours improved dyspnea with more rapid relief of congestion during the first days after admission for heart failure. In addition, administration of serelaxin diminished cardiac, renal, and hepatic damage, which were associated with improved long-term mortality. Available data support substantial clinical benefits and significant promise for serelaxin as a treatment option for patients with acute heart failure. This review focuses on the pharmacology and mechanisms of action of serelaxin and provides a detailed discussion of the clinical evidence for this novel therapy in acute heart failure.

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“…Dschietzig et al [25] reported that relaxin-2 is a positive inotrope in non-failing and failing human atria, with critical involvement of protein kinase A and inhibition of the transient potassium outward current and an increasing role for G(i) protein-PI3K signaling in failing myocardium. Clinical studies have examined changes in circulating relaxin and its possible role as a diagnostic marker for patients with cardiovascular diseases (Table 1).…”

mentioning

confidence: 98%