2. Academic Validation
  3. Serelaxin has greater anti-fibrotic potential than perindopril but maintains its anti-fibrotic efficacy in the presence of perindopril in normotensive mouse models of heart disease

Serelaxin has greater anti-fibrotic potential than perindopril but maintains its anti-fibrotic efficacy in the presence of perindopril in normotensive mouse models of heart disease

  • Life Sci. 2026 Aug 15:399:124472. doi: 10.1016/j.lfs.2026.124472.
Ziqiao Wang 1,  Gang She 2,  Chao Wang 1,  Dorota Ferens 3,  Ekaterina Salimova 4,  Robert E Widdop 3,  Tracey A Gaspari 3,  Chrishan S Samuel 5
Affiliations

Affiliations

  • 1 Fibrosis Group, Department of Pharmacology and Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • 2 Fibrosis Group, Department of Pharmacology and Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 3 Integrative Cardiovascular Pharmacology Group, Department of Pharmacology and Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • 4 Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
  • 5 Fibrosis Group, Department of Pharmacology and Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. Electronic address: [email protected].
PMID: 42176886 DOI: 10.1016/j.lfs.2026.124472
Abstract

Aims: Serelaxin (RLX), the drug form of human gene-2 relaxin, has potent anti-fibrotic properties that are currently being clinically-evaluated for the treatment of heart failure (HF). Whilst these effects can potentially be antagonised by Angiotensin Receptor blocker co-administration, this study determined if RLX was a suitable adjunct therapy to angiotensin converting enzyme inhibitor (ACEi) treatment. In particular, the anti-fibrotic effects of RLX were compared to or combined with the clinically-used ACEi, perindopril, in murine models of isoprenaline (ISO)-induced cardiomyopathy and surgically-induced myocardial infarction (MI).

Methods: The dose-response effects of perindopril (1, 2 or 4 mg/kg/day) on systolic blood pressure (SBP) and left ventricular (LV) fibrosis were first assessed in ISO-injured mice, after 7- or 14-days of treatment. The therapeutic effects of RLX (0.5 mg/kg/day) on SBP, LV fibrosis and LV functional parameters (ejection fraction, fractional shortening, stroke volume, cardiac output) were then compared to or combined with perindopril (2 mg/kg/day) pre-treatment (7-days prior) or co-administration (over 7-days) in ISO-injured mice; or perindopril co-administration (over 21-days) in MI-injured mice.

Key findings: Perindopril attenuated the ISO-induced LV fibrosis at 2 or 4 mg/kg/day, but induced significant hypotension at 4 mg/kg/day. RLX reduced the ISO- or MI-induced LV fibrosis, and restored measures of LV dysfunction, to a greater extent than perindopril (2 mg/kg/day), in the absence of BP regulation. These effects were maintained in the presence of perindopril pre-treatment or co-administration.

Significance: These findings confirmed that RLX had greater anti-fibrotic potential than perindopril, but could be applied as a rapidly-acting adjunct therapy to ACEi.

Keywords

ACEi; Cardiomyopathy; Fibrosis; Myocardial infarction; RXFP1; Relaxin.

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