title: Novel perspectives on the PHD-HIF oxygen sensing pathway in cardioprotection mediated by IPC and RIPC.
abstract: Reperfusion of ischemic cardiac tissue is the standard treatment for improving clinical outcome following myocardial infarction but is inevitably associated with ischemia-reperfusion injury (IRI). Ischemic myocardial injury can be alleviated by exposing the heart to brief episodes of sublethal ischemia-reperfusion prior to the ischemic insult, a phenomenon that has been termed ischemic preconditioning (IPC). Similarly, remote IPC (RIPC) is defined as transient episodes of ischemia at a distant site before a subsequent prolonged injury of the target organ. In this setting, adaptive responses to hypoxia/ischemia in peripheral tissues include the release of soluble factors that have the potential to protect cardiomyocytes remotely. Oxygen fluctuations is a hallmark of insufficient tissue perfusion and ischemic episodes. Emerging evidence indicates that prolyl hydroxylase oxygen sensors (PHDs) and hypoxia-inducible transcription factors (HIFs) are critical regulators of IPC and RIPC. In this review, we discuss recent findings concerning the role of the PHD-HIF axis in IPC and RIPC-mediated cardioprotection and examine molecular pathways and cell types that might be involved. We also appraise the therapeutic value of targeting the PHD-HIF axis to enhance cardiac tolerance against IRI.
authors.affiliation: Cell and Developmental Biology Department, Centro Nacional de Investigaciones Cardiovasculares Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Martin-Puig
authors.affiliation: Research Unit, Hospital Santa Cristina, Research Institute Princesa (IP), Autonomous University of Madrid Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tello
authors.affiliation: Research Unit, Hospital Santa Cristina, Research Institute Princesa (IP), Autonomous University of Madrid Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Aragonés
keywords: PHD oxygen sensors; heart; hypoxia-inducible factors; ischemic preconditioning; remote ischemic preconditioning