B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin)

This study investigated B7-33, a simplified single-chain peptide derived from the B chain of human relaxin-2 (serelaxin), as a potential therapeutic analog with preserved vasoprotective functions. Relaxin-2 is a complex heterodimeric peptide hormone (two chains, A and B, linked by disulfide bonds) whose synthesis is costly, which limits its broad clinical application.

B7-33 was tested in isolated mesenteric arteries from rats and in models of vascular oxidative stress. The peptide demonstrated the ability to induce endothelium-dependent vasodilation with potency comparable to serelaxin, while retaining anti-fibrotic properties — the ability to reduce excessive collagen deposition in vascular tissues. These effects were mediated by selective activation of the RXFP1 receptor (relaxin family peptide receptor 1).

A particularly interesting finding was that B7-33 exerted its vasoprotective effects without increasing cAMP production (cyclic adenosine monophosphate), unlike native relaxin-2. This indicates that B7-33 is a functionally selective agonist (or "biased agonist") of RXFP1, preferentially activating signaling pathways responsible for vasoprotection while avoiding other intracellular cascades.

The importance of this work lies in demonstrating that a single-chain peptide, structurally much simpler than native relaxin-2, can reproduce the most relevant therapeutic functions of the hormone. This opens the way for the development of accessible peptide analogs for the treatment of cardiovascular diseases, fibrosis, and preeclampsia.