Related Experiment Video
Updated: Mar 9, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Serelaxin treatment reverses vascular dysfunction and left ventricular hypertrophy in a mouse model of Type 1
Hooi Hooi Ng1,2, Chen Huei Leo1, Darnel Prakoso1,2
1School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia.
Abstract:
Serelaxin prevents endothelial dysfunction in the mouse aorta ex vivo and inhibits apoptosis in cardiomyocytes under acute hyperglycaemia. Less is known about the effects of serelaxin in an in vivo mouse model of diabetes. Therefore, we tested the hypothesis in streptozotocin (STZ)-treated mice that serelaxin is able to reverse diabetes-induced vascular dysfunction and cardiac remodelling. Mice were divided into citrate buffer + placebo, STZ + placebo and STZ + serelaxin (0.5 mg/kg/d, 2 weeks) groups. After 12 weeks of diabetes, sensitivity to the endothelium-dependent agonist acetylcholine (ACh) was reduced in the mesenteric artery. This was accompanied by an enhanced vasoconstrictor prostanoid contribution and a decrease in endothelium-derived hyperpolarisation (EDH)-mediated relaxation. Serelaxin restored endothelial function by increasing nitric oxide (NO)-mediated relaxation but not EDH. It also normalised the contribution of vasoconstrictor prostanoids to endothelial dysfunction and suppressed diabetes-induced hyper-responsiveness of the mesenteric artery to angiotensin II. Similarly, diabetes reduced ACh-evoked NO-mediated relaxation in the aorta which was reversed by serelaxin. In the left ventricle, diabetes promoted apoptosis, hypertrophy and fibrosis; serelaxin treatment reversed this ventricular apoptosis and hypertrophy, but had no effect on fibrosis. In summary, serelaxin reversed diabetes-induced endothelial dysfunction by enhancing NO-mediated relaxation in the mouse vasculature and attenuating left ventricular hypertrophy and apoptosis.
Insights
Serelaxin treatment reversed diabetes-induced vascular dysfunction and cardiac remodeling in mice. It improved nitric oxide-mediated relaxation and reduced left ventricular hypertrophy and apoptosis.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus is associated with endothelial dysfunction and cardiac remodeling.
- Serelaxin's effects in a chronic in vivo diabetes model are not well understood.
- Previous studies showed serelaxin's benefits ex vivo and in acute hyperglycemia.
Purpose of the Study:
- To investigate if serelaxin can reverse diabetes-induced vascular dysfunction and cardiac remodeling in vivo.
- To test the hypothesis that serelaxin improves endothelial function and cardiac structure in a mouse model of diabetes.
Main Methods:
- Streptozotocin (STZ)-induced diabetes mouse model.
- Treatment groups: citrate buffer + placebo, STZ + placebo, STZ + serelaxin (0.5 mg/kg/d for 2 weeks).
- Assessment of vascular function (mesenteric artery, aorta) and cardiac remodeling (left ventricle) after 12 weeks.
Main Results:
- Serelaxin restored acetylcholine-induced relaxation in mesenteric arteries and aorta by enhancing nitric oxide (NO)-mediated relaxation.
- Serelaxin normalized vasoconstrictor prostanoid contribution and suppressed angiotensin II hyper-responsiveness.
- Serelaxin reversed diabetes-induced left ventricular apoptosis and hypertrophy, but not fibrosis.
Conclusions:
- Serelaxin effectively reverses diabetes-induced endothelial dysfunction in mice by enhancing NO-mediated relaxation.
- Serelaxin attenuates cardiac hypertrophy and apoptosis in a mouse model of diabetes.
- These findings suggest serelaxin's therapeutic potential for diabetic vascular and cardiac complications.
