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Updated: Jun 5, 2025
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
The Metabolically Resistant Apelin-17 Analogue LIT01-196 Reduces Cardiac Dysfunction and Remodelling in Heart Failure
Pierre-Emmanuel Girault-Sotias1, Robin Deloux2, Nadia De Mota3
1Laboratory of Central Neuropeptides in the Regulation of Water Balance and Cardiovascular Functions, College de France, CIRB, INSERM U1050/CNRS UMR7241, 75005 Paris, France. Electronic address: https://twitter.com/PiGirault.
A new apelin analogue, LIT01-196, improved heart function after myocardial infarction (MI) in mice. This therapeutic approach enhanced cardiac repair and may offer a novel treatment for heart failure (HF) post-MI.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Biomedical Science
Background:
- Developing new therapeutics to preserve cardiac function post-myocardial infarction (MI) is crucial.
- Apelin peptide offers benefits but has a short in vivo half-life.
- A metabolically resistant apelin-17 analogue, LIT01-196, was developed to overcome this limitation.
Purpose of the Study:
- To investigate the effects of LIT01-196 on cardiac function and remodeling in a murine MI model.
- To assess the therapeutic potential of apelin receptor activation in post-MI heart failure (HF).
Main Methods:
- In vitro selectivity and in vivo half-life assessment of LIT01-196.
- Subcutaneous administration of LIT01-196 or vehicle in a murine MI model for 4 weeks.
- Evaluation of left ventricular (LV) function, vascular density, cardiac fibrosis, and gene expression.
Main Results:
- LIT01-196 demonstrated a half-life of 2.5 hours and selectively activated the apelin receptor.
- Treatment significantly improved LV function, cardiac contractility, and SERCA2 expression.
- LIT01-196 doubled cardiac vascular density, reduced fibrosis, and maintained LV wall thickness without lowering blood pressure.
Conclusions:
- Chronic LIT01-196 treatment post-MI improves LV function and cardiac remodeling.
- Apelin receptor activation by LIT01-196 increases vascular density and reduces fibrosis.
- LIT01-196 represents a potential novel pharmacological approach for treating heart failure after myocardial infarction.
