Why do we still not have cardioprotective drugs to prevent post-MI heart failure? Need for unbiased “omics” approach and co-morbidity models to find valid targets.

Ischemic heart disease is the leading cause of mortality worldwide, therefore, identification of valid drug targets for cardioprotection and thereby prevention of post-infarction heart failure is of great importance. The discovery of ischemic preconditioning 3 decades ago, postconditioning, and remote conditioning triggering endogenous cardioprotective mechanisms that render the heart more resistant to lethal ischemic-reperfusion injury gave much hope to identify cardioprotective drug targets. However, despite the several development projects that reached clinical phases, there are still no cardioprotective drugs on the market. Recent progress in cardioprotection revealed that major cardiovascular co-morbidities such as hyperlipidemia, diabetes, and their co-medications interferes with most of the currently known cardioprotective mechanisms. Moreover, ischemia reperfusion injury and cardioprotection by ischemic conditioning have been shown to affect global myocardial gene expression profile at the transcript level. Fine tuning regulators of mRNA expression, miRNAs also contribute to cardioprotective gene expression response of the heart. Cardiovascular co-morbidities have been also shown to affect global cardiac gene expression profile. Further understanding and the comprehensive network analysis of the cardioprotective gene expression fingerprint at the transcript and protein level in normal, protected, and in comorbid conditions may lead to identification of novel molecular targets for cardioprotection.