SelenoproteinT43-52 as a cardioprotector
Myocardial infarction occurs when the blood supply to part of the heart is interrupted causing cells death. The immediate goal is to restore blood flow. However, this may lead to a ischemia-reperfusion (I/R) injury. Successful cardioprotection is limited by a small number of therapeutic targets. The inventors showed that a SelenoproteinT-derived peptide 43-52 is effective against I/R injury.
The inventors aim to determine the expression and regulation of SelT in the mammalian rat heart in normal and pathological conditions, and to evaluate the cardioprotective effect of a SelT-derived peptide43-52 (PSELT) encompassing the redox motif of SelT which is key to its function, against I/R injury. The inventors found that SelT expression is more abundant in embryo than newborn heart and is undetectable in adult. SelT expression was increased after I/R, suggesting a protective role after an insult. By using the PSELT, inventors demonstrated that PSELT (5 nM) induced post-conditioning cardioprotection by a significant recovery of contractility, without changes in cardiac contracture, and by a significant reduction of infarct size. PSELT-dependent cardioprotection is accompanied by a significant increase of expression of pro-survival kinases and by inhibition of apoptosis and reduction of oxidative and nitrosative stress.
- Administration to a subject having one or more signs or symptoms of acute myocardial infarction injury;
- Simultaneously or sequentially administration (i.e. before/after) with a revascularization procedure performed on the subject;
- Administration in combination with an additional active agent.
- PSELT peptide is synthetized by any well-known method in art;
- PSELT peptide is the functional motif of the endogenous protein Selenoprotein T;
- PSELT peptide determines cardioprotection at physiological doses.