Castrini Anna Isotta, Carubelli Valentina, Lazzarini Valentina, Bonadei Ivano, Lombardi Carlo, Metra Marco
a Department of Medical and Surgical Specialties, Cardiology, Radiological Sciences, and Public Health, University and Civil Hospital of Brescia, Brescia, Italy.
Expert Rev Clin Pharmacol. 2015;8(5):549-57. doi: 10.1586/17512433.2015.1073587.
Acute heart failure (AHF) represents a major healthcare burden with a high risk of in-hospital and post-discharge mortality, which remained almost unchanged in the last few decades, underscoring the need of new treatments. Relaxin is a naturally occurring human peptide initially identified as a reproductive hormone and has been shown to play a key role in the maternal hemodynamic and renal adjustments that accommodate pregnancy. Recently, the new molecule serelaxin, a recombinant form of the naturally occurring hormone relaxin has been studied in patients hospitalized for AHF. In addition to vasodilation, serelaxin has anti-oxidative, anti-inflammatory and connective tissue regulating properties. In preclinical studies, it reduced both systemic and renal vascular resistance and, in the clinical trials Pre-RELAX-AHF and RELAX-AHF, it improved dyspnea and signs of congestion. In addition, serelaxin was associated with a reduction of 180-day mortality. The aim of this review is to summarize the pharmacological properties of serelaxin and the results of the preclinical and clinical studies.
急性心力衰竭(AHF)是一项重大的医疗负担,具有较高的住院和出院后死亡风险,在过去几十年中几乎没有变化,这凸显了新治疗方法的必要性。松弛素是一种天然存在的人体肽,最初被鉴定为一种生殖激素,已被证明在适应妊娠的母体血液动力学和肾脏调节中起关键作用。最近,新型分子重组松弛素(serelaxin),即天然激素松弛素的重组形式,已在因AHF住院的患者中进行了研究。除血管舒张作用外,重组松弛素还具有抗氧化、抗炎和调节结缔组织的特性。在临床前研究中,它降低了全身和肾血管阻力,并且在PRE-RELAX-AHF和RELAX-AHF临床试验中,它改善了呼吸困难和充血症状。此外,重组松弛素与180天死亡率的降低相关。本综述的目的是总结重组松弛素的药理学特性以及临床前和临床研究的结果。