Endogenous Cardioprotective Agents: Role in Pre and Postconditioning

Abstract

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.

Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway

“…The cardioprotective action of obestatin, when infused at the early reperfusion, expands our previous observations on the positive effects of the peptide when given before an ischaemic event [15]. As treatments at the onset of myocardial reperfusion are more feasible than pre-treatments [55][56][57], the present results may have a greater relevance, in view of its possible clinical application.…”

Hyperglycemia Abrogates Ischemic Postconditioning Cardioprotection by Impairing AdipoR1/Caveolin-3/STAT3 Signaling in Diabetic Rats

“…NO represents one of the most important defense mechanisms against MIRI and is also one of the major mediators of IPo cardioprotection (36). In the current study, IPo conferred cardioprotective effects through APN that was associated with reduced postischemic nitrotyrosine formation and increased cardiac NO production in WT but not in Adipo 2/2 mice.…”

Platelets, diabetes and myocardial ischemia/reperfusion injury

“…These brief notes are useful to better understand the following paragraphs. The reader is kindly redirected to specific literature for more details regarding the cardioprotective pathways activated by conditioning procedures [52–55]. …”