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 had greater anti-fibrotic potential than perindopril and maintained its anti-fibrotic efficacy in the presence of perindopril pre-treatment or co-administration in normotensive mouse models of heart disease.
Key Findings
Results
Perindopril attenuated ISO-induced left ventricular fibrosis at 2 or 4 mg/kg/day but induced significant hypotension at the highest dose.
Three doses of perindopril were assessed: 1, 2, or 4 mg/kg/day in isoprenaline (ISO)-injured mice
Only the 2 and 4 mg/kg/day doses produced significant anti-fibrotic effects on left ventricular (LV) fibrosis
Perindopril at 4 mg/kg/day induced significant hypotension, making it unsuitable for normotensive heart disease models
Effects were assessed after 7 or 14 days of treatment
Results
Serelaxin reduced ISO-induced LV fibrosis to a greater extent than perindopril (2 mg/kg/day) without affecting blood pressure.
Serelaxin was administered at 0.5 mg/kg/day
Perindopril was used at 2 mg/kg/day for comparison, a dose selected to avoid significant hypotension
Serelaxin's anti-fibrotic effects occurred in the absence of blood pressure regulation
Treatment comparison was conducted in the ISO-induced cardiomyopathy model
Results
Serelaxin reduced MI-induced LV fibrosis to a greater extent than perindopril (2 mg/kg/day) in a surgically-induced myocardial infarction model.
The myocardial infarction (MI) model involved surgical induction of injury
Perindopril co-administration occurred over 21 days in the MI model
Serelaxin again demonstrated superior anti-fibrotic efficacy compared to perindopril at 2 mg/kg/day
This further confirmed serelaxin's greater anti-fibrotic potential across two distinct disease models
Results
Serelaxin restored measures of left ventricular dysfunction to a greater extent than perindopril (2 mg/kg/day).
LV functional parameters assessed included ejection fraction, fractional shortening, stroke volume, and cardiac output
Serelaxin outperformed perindopril on these functional measures in ISO-injured mice
These functional improvements occurred without blood pressure regulation by serelaxin
Results
Serelaxin maintained its anti-fibrotic efficacy in the presence of perindopril pre-treatment or co-administration in ISO-injured mice.
Two combination regimens were tested: perindopril pre-treatment (7 days prior to serelaxin) and perindopril co-administration (over 7 days simultaneously with serelaxin)
Serelaxin's anti-fibrotic effects were not antagonized by ACE inhibitor co-treatment
This is in contrast to previously described antagonism between serelaxin and angiotensin receptor blockers
Perindopril was used at 2 mg/kg/day in combination studies
Results
Serelaxin maintained its anti-fibrotic efficacy when combined with perindopril co-administration over 21 days in MI-injured mice.
The MI model combination study ran for 21 days of co-administration
Serelaxin's anti-fibrotic properties were preserved in the presence of the ACEi in the MI setting
These findings support the feasibility of serelaxin as a rapidly-acting adjunct therapy to ACE inhibitor treatment
Methods
The study was conducted in normotensive mouse models to reflect a patient population where blood pressure lowering may not be appropriate.
Both isoprenaline-induced cardiomyopathy and surgically-induced myocardial infarction models were used as normotensive heart disease models
The study context was relevant because serelaxin does not regulate blood pressure in these models
The normotensive setting distinguished the anti-fibrotic mechanism from hemodynamic effects
Serelaxin is currently being clinically evaluated for heart failure treatment
What This Means
This research suggests that serelaxin, a drug based on a naturally occurring human hormone called relaxin, is more effective than a standard heart medication (perindopril, a type of ACE inhibitor) at reducing harmful scarring (fibrosis) in the heart and improving heart function in mouse models of heart disease. Importantly, serelaxin achieved these benefits without lowering blood pressure, which is relevant for patients who already have normal or low blood pressure and cannot tolerate further reductions. The study tested two types of heart injury in mice — one caused by a drug (isoprenaline) and one caused by a simulated heart attack — and found serelaxin outperformed perindopril in both settings.
A key practical finding was that serelaxin retained its anti-scarring effects even when given alongside perindopril, whether perindopril was started first or given at the same time. This is significant because previous research had shown that another class of blood pressure drugs (angiotensin receptor blockers) could actually block serelaxin's beneficial effects. This study shows that ACE inhibitors like perindopril do not have this antagonistic interaction, suggesting the two drugs can be safely used together.
This research suggests that serelaxin could potentially be used as an add-on therapy for heart failure patients who are already taking ACE inhibitors — one of the most commonly prescribed drug classes for heart conditions. If these findings translate to humans, serelaxin might offer an additional layer of heart protection beyond what ACE inhibitors alone can provide, particularly for patients who need anti-fibrotic treatment but cannot tolerate blood pressure-lowering side effects.
Wang Z, She G, Wang C, Ferens D, Salimova E, Widdop R, et al.. (2026). 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 sciences. https://doi.org/10.1016/j.lfs.2026.124472