Endogenous Cardioprotective Agents: Role in Pre and Postconditioning.

Cardiovascular diseases (CVD) are the leading cause of death, chronic illness and disability in Western countries. The most common cause of CVD derives from the harmful effects of acute myocardial ischemia and subsequent reperfusion injury. Cardioprotection against acute ischemia/ reperfusion injury is made possible by the "conditioning protocols." Conditioning is obtained by applying a few periods of brief ischemia and reperfusion in the event of prolonged (index) ischemia that may cause myocardial infarction. Whilst the conditioning stimulus is applied before the index ischemia in ischemic pre-conditioning, it is applied after the event in post-conditioning. Pre and post- conditioning stimuli can be applied in a different/remote organ (remote pre- and post-conditioning); in this case conditioning stimulus can also be applied during the index event, in the so called remote per-conditioning. All these endogenous cardioprotective strategies recruit endogenous cytoprotective agents and factors that elicit specific cardioprotective pathways. Here, we discuss many of these cardioprotective factors compared to literature and highlight their main characteristics and mechanisms of action. Enphasis is given to endogenous cardioprotective agents acting or not on surface receptors, including chromogranin A derivatives, ghrelin-associated peptides, growth factors and cytokines, and to microvesicles and exosomes. Moreover the cardioprotective effects of gasotransmitters nitric oxide, hydrogen sulphide and carbon monoxide are reviewed. The possible clinical translation of these knowledge for future successful therapies is briefly and critically discussed.