title: The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning.
abstract: Ischaemic heart disease is one of the leading causes of morbidity and mortality worldwide. The development of cardioprotective therapeutic agents remains a partly unmet need and a challenge for both medicine and industry, with significant financial and social implications. Protection of the myocardium can be achieved by mechanical vascular occlusions such as preconditioning (PC), when brief episodes of ischaemia/reperfusion (I/R) are experienced prior to ischaemia; postconditioning (PostC), when the brief episodes are experienced at the immediate onset of reperfusion; and remote conditioning (RC), when the brief episodes are experienced in another vascular territory. The elucidation of the signalling pathways, which underlie the protective effects of PC, PostC and RC, would be expected to reveal novel molecular targets for cardioprotection that could be modulated by pharmacological agents to prevent reperfusion injury. Gasotransmitters including NO, hydrogen sulphide (H2S) and carbon monoxide (CO) are a growing family of regulatory molecules that affect physiological and pathological functions. NO, H2S and CO share several common properties; they are beneficial at low concentrations but hazardous in higher amounts; they relax smooth muscle cells, inhibit apoptosis and exert anti-inflammatory effects. In the cardiovascular system, NO, H2S and CO induce vasorelaxation and promote cardioprotection. In this review article, we summarize current knowledge on the role of the gasotransmitters NO, H2S and CO in myocardial I/R injury and cardioprotection provided by conditioning strategies and highlight future perspectives in cardioprotection by NO, H2S, CO, as well as their donor molecules.
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, University of Athens, Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.forename: Efstathios K
authors.initials: EK
authors.lastname: Iliodromitis
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Andreas
authors.initials: A
authors.lastname: Papapetropoulos
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D064426:Gasotransmitters / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D057775:Ischemic Postconditioning / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D058990:Molecular Targeted Therapy; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000628:therapy; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D064426:Gasotransmitters; D009569:Nitric Oxide; D006862:Hydrogen Sulfide