Acute myocardial infarction (AMI) is a frequent and disabling disease, which is the first cause of cardiovascular mortality
worldwide. Infarct size is a major determinant of myocardial functional recovery and mortality after AMI. Limitation of infarct size thus
appears as an appropriate strategy to prevent post-ischemic heart failure and improve survival. Reperfusion is the only treatment recommended
to reduce infarct size but despite obvious benefits, it may also have deleterious effects called ischemia-reperfusion (IR) injury including
myocyte cell death.
Proteins involved in the apoptosis cascade generally interact over large surfaces lacking well-defined pockets. Therefore, inhibitory peptides
are optimal biomolecules to target these large protein surfaces, they are often more selective to their target than conventional small
organic molecules, and they can be tailored for optimal affinity or desired metabolic property. Since peptides do not cross freely biological
membranes, they are generally administered in association with cell penetrating peptides (CPPs) and with homing peptides (HPs) for
selective organs or tissues targeting. As a first approach in vivo, we made use of the already known BH4 peptidic inhibitor of the mitochondrial
apoptotic pathway, which showed cardioprotective properties in a murine model of AMI after a single bolus of intravenous
More importantly, similar peptidic strategies and tools are likely to be adaptable to many other situations in which cells have to be protected
from apoptosis such as stroke or organ transplantation.