Cardiovascular effects of relaxin: from basic science to clinical therapy.

Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Vic 3008, Australia.
Nature Reviews Cardiology (Impact Factor: 10.4). 11/2009; 7(1):48-58. DOI: 10.1038/nrcardio.2009.198
Source: PubMed

ABSTRACT Although substantial advances have been achieved in recent decades in the clinical management of heart diseases, new therapies that provide better or additional efficacy with minimal adverse effects are urgently required. Evidence that has accumulated since the 1990s indicates that the peptide hormone relaxin has multiple beneficial actions in the cardiovascular system under pathological conditions and, therefore, holds promise as a novel therapeutic intervention. Clinical trials for heart failure therapy using relaxin revealed several beneficial actions. Here we review findings from mechanistic and applied research in this field, comment on the outcomes of recent phase I/II clinical trails on patients with heart failure, and highlight settings of cardiovascular diseases where relaxin might be effective.

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    ABSTRACT: Relaxin, a new drug for heart failure therapy, exerts its cardiac actions through relaxin family peptide receptor 1 (RXFP1). Factors regulating RXFP1 expression remain unknown. We have investigated effects of activation of adrenoceptors (AR), an important modulator in the development and prognosis of heart failure, on expression of RXFP1 in rat cardiomyocytes and mouse left ventricles (LV).
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    ABSTRACT: Introduction: Despite the improvement in heart failure (HF) therapy in the last 30 years, this condition remains a major public health concern with high hospitalization and mortality rates, and related costs. Recently, new pharmacological approaches are under evaluation. Areas covered: For chronic HF with reduced ejection fraction (EF) direct renin inhibitors, neprilysin-angiotensin II receptor inhibitors and aldosterone synthase inhibitors have been tested. For HF with preserved EF, no therapy has been demonstrated up to now to be able to improve patients' outcomes and it remains a substantial unmet need. In acute HF (AHF) new inotropes and vasodilators have been developed and are currently investigated in trials. In this review, mechanism of action and clinical efficacy of new pharmacological approaches on acute and chronic HF will be discussed. Expert opinion: In patients with HF, some unmet needs remain to be challenged in the near future. For patients with chronic HF, the management of comorbidities, a better definition and treatment of patients with preserved EF are the major issues to be solved. The treatment of patients admitted for AHF is even more compelling. Several hypotheses of research focused on these issues are tested in ongoing trials.
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