Delayed phospholamban phosphorylation in post-conditioned heart favours Ca2+ normalization and contributes to protection

Inserte, Javier; Hernando, Víctor; Ruiz‐Meana, Marisol; Poncelas‐Nozal, Marcos; Fernandez, Celia G.; Agulló, Luís; Sartorio, Carmem Lluisa; Vilardosa, Úrsula; Garcı́a-Dorado, David

doi:10.1093/cvr/cvu163

Cited by 31 publications

(23 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the patch-clamp experiments, BAY41-2272 could influence both the whole-cell K + currents and BK Ca currents, and the effect of BAY41-2272 on SMCs in the HS group was weaker than that in the NS. In the presence of KT5823, a specific PKG inhibitor [31], the effect of BAY41-2272 on the K + currents was blocked in both groups. This suggested that the activation of K + currents via sGC needed participation of PKG.…”

Section: Discussionmentioning

confidence: 93%

High-salt diets during pregnancy increases renal vascular reactivity due to altered soluble guanylyl cyclase-related pathways in rat offspring

Lin

Yin

et al. 2016

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 93%

High-salt diets during pregnancy increases renal vascular reactivity due to altered soluble guanylyl cyclase-related pathways in rat offspring

Lin

Yin

et al. 2016

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

“…Additionally, our study suggests that cGMP/PKG‐dependent activation of PDE2 is responsible for the inhibition of PKA while the reduced activity of CaMKII could be the result of PoCo‐dependent attenuation of Ca 2+ overload and ROS production during the first minutes of reperfusion (Erickson et al ., ). The resulting blockade of SERCA activity during the first minutes of reperfusion attenuated the development of hypercontracture and cell death by preventing Ca 2+ oscillations and allowed for Ca 2+ normalization through the Na + /Ca 2+ exchanger and for the activation of endogenous protective signalling pathways that ensure long‐term cardioprotection (Inserte et al ., ).…”

Section: Cgmp/pkg Pathway As a Mediator Of Endogenous Cardioprotectionmentioning

confidence: 97%

The cGMP/PKG pathway as a common mediator of cardioprotection: translatability and mechanism

Inserte

Garcı́a-Dorado

2015

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

Cardiomyocyte cell death occurring during myocardial reperfusion (reperfusion injury) contributes to final infarct size after transient coronary occlusion. Different interrelated mechanisms of reperfusion injury have been identified, including alterations in cytosolic Ca 2+ handling, sarcoplasmic reticulum-mediated Ca 2+ oscillations and hypercontracture, proteolysis secondary to calpain activation and mitochondrial permeability transition. All these mechanisms occur during the initial minutes of reperfusion and are inhibited by intracellular acidosis. The cGMP/PKG pathway modulates the rate of recovery of intracellular pH, but has also direct effect on Ca 2+ oscillations and mitochondrial permeability transition. The cGMP/PKG pathway is depressed in cardiomyocytes by ischaemia/reperfusion and preserved by ischaemic postconditioning, which importantly contributes to postconditioning protection. The present article reviews the mechanisms and consequences of the effect of ischaemic postconditioning on the cGMP/PKG pathway, the different pharmacological strategies aimed to stimulate it during myocardial reperfusion and the evidence, limitations and promise of translation of these strategies to the clinical practice. Overall, the preclinical and clinical evidence suggests that modulation of the cGMP/PKG pathway may be a therapeutic target in the context of myocardial infarction. LINKED ARTICLESThis article is part of a themed section on Conditioning the Heart -Pathways to Translation. To view the other articles in this section visit http://dx.doi. org/10.1111/bph.2015.172.issue-8 Abbreviations AMI, acute myocardial infarction; ANP, atrial natriuretic peptide; BH4, tetrahydrobiopterin; CaMK, Ca 2+ /calmodulin-dependent PK; eNOS, endothelial NOS; GIK, glucose-insulin-potassium; GLP-1, glucagon-like peptide-1; GSK3β, glycogen synthase kinase-3β; mPTP, mitochondrial permeability transition pore; NHE, Na+/H + exchanger; NP, natriuretic peptide; ODQ, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one; PCI, percutaneous coronary intervention; pGC, particulate GC; pHi, intracellular pH; PLB, phospholamban; PoCo, ischaemic postconditioning; PreC, ischaemic preconditioning; RIC, remote ischaemic conditioning; RISK, reperfusion injury salvage kinases; ROS, reactive oxygen species; SERCA, sarcoplasmic reticulum Ca Ischaemia/reperfusion injuryCardiomyocyte death is the main cause of the mortality and morbidity in patients with ischaemic heart disease, the leading cause of death in the global world population. It occurs mainly during the acute coronary syndrome, and in particular during myocardial infarction with ST-segment elevation, for which the main treatment is prompt reperfusion. There is solid evidence supporting that part of cell death, secondary to transient coronary occlusion, occurs upon restoration of coronary blood flow, a phenomenon known as reperfusion injury (Piper et al., 1998;Yellon and Hausenloy, 2007). The mechanisms responsible for cell death during myocardial reperfusion are complex but progressively better k...

show abstract

“…398 The sarcoplasmic reticulum is a target of PKCε 185 and of protein nitrosylation, 399 POC delays phosphorylation of phospholamban by PKG, and reduced sarcoplasmic reticulum ATPase activity in the presence of acidosis favors the extrusion of cytosolic calcium through the sodium-calcium exchanger and reduces calcium oscillations, thus contributing to reduced IS. 400 Cytoskeleton, Cell Volume, and Ionic Balance Decreased cytoskeletal stability and increased cell volume contribute to membrane disruption and cellular fragility. IPC attenuates osmotic fragility through cytochalasin D-sensitive stabilization of the actin cytoskeleton and a K ATP -dependent mechanism in isolated rabbit cardiomyocytes.…”

Section: Heusch Signal Transduction Of Conditioning 683mentioning

confidence: 99%

Molecular Basis of Cardioprotection

Heusch

2015

Circulation Research

704

409

View full text Add to dashboard Cite

Abstract:Reperfusion is mandatory to salvage ischemic myocardium from infarction, but reperfusion per se contributes to injury and ultimate infarct size. Therefore, cardioprotection beyond that by timely reperfusion is needed to reduce infarct size and improve the prognosis of patients with acute myocardial infarction. The conditioning phenomena provide such cardioprotection, insofar as brief episodes of coronary occlusion/ reperfusion preceding (ischemic preconditioning) or following (ischemic postconditioning) sustained myocardial ischemia with reperfusion reduce infarct size. Even ischemia/reperfusion in organs remote from the heart provides cardioprotection (remote ischemic conditioning). The present review characterizes the signal transduction underlying the conditioning phenomena, including their physical and chemical triggers, intracellular signal transduction, and effector mechanisms, notably in the mitochondria. Cardioprotective signal transduction appears as a highly concerted spatiotemporal program. Although the translation of ischemic postconditioning and remote ischemic conditioning protocols to patients with acute myocardial infarction has been fairly successful, the pharmacological recruitment of cardioprotective signaling has been largely disappointing to date.

show abstract

Delayed phospholamban phosphorylation in post-conditioned heart favours Ca2+ normalization and contributes to protection

Cited by 31 publications

References 48 publications

High-salt diets during pregnancy increases renal vascular reactivity due to altered soluble guanylyl cyclase-related pathways in rat offspring

High-salt diets during pregnancy increases renal vascular reactivity due to altered soluble guanylyl cyclase-related pathways in rat offspring

The cGMP/PKG pathway as a common mediator of cardioprotection: translatability and mechanism

Molecular Basis of Cardioprotection

Contact Info

Product

Resources

About