Relaxin-2
Cardiovascular / ReproductiveAlso known as: Human Relaxin-2, H2 Relaxin, RLN2, Serelaxin
Mechanism
Relaxin-2 is a pregnancy hormone that relaxes blood vessels and softens connective tissue. It increases blood flow to the kidneys and heart, reduces blood pressure, and promotes tissue remodeling. Serelaxin (recombinant relaxin-2) was investigated for acute heart failure but narrowly failed Phase 3 trials, despite promising Phase 2 results showing reduced mortality.
Technical detail
Relaxin-2 is a 6 kDa heterodimeric peptide (A and B chains linked by disulfide bonds) structurally related to insulin. It signals through RXFP1 (LGR7), a leucine-rich repeat GPCR that activates Gs-cAMP, PI3K-Akt-eNOS, and Erk1/2 pathways. Vascular effects include endothelium-dependent vasodilation via NO and endothelin receptor type B, increased renal blood flow and GFR, and arterial compliance. Anti-fibrotic effects involve inhibition of TGF-beta/Smad2 signaling and MMP upregulation for collagen degradation. Serelaxin (recombinant form) failed Phase 3 RELAX-AHF-2 trial for acute heart failure despite positive Phase 2 signal.
Evidence
- strong
Effects of serelaxin in patients admitted for acute heart failure: a meta-analysis
Teerlink et al. (2020) — European Journal of Heart Failure — PMID: 31886953
Meta-analysis of six randomized acute heart failure trials found serelaxin reduced 5-day worsening heart failure and improved renal biomarkers, without clear benefit on cardiovascular death or rehospitalization.
- strong
Effects of Serelaxin in Patients with Acute Heart Failure
Metra et al. (2019) — The New England Journal of Medicine — PMID: 31433919
Large placebo-controlled acute heart failure trial found serelaxin did not significantly reduce 180-day cardiovascular death or 5-day worsening heart failure versus placebo, providing important negative but high-quality clinical evidence for relaxin-2 pathway therapy.