Urocortin 2 protects heart and kidney structure and function in an ovine model of acute decompensated heart failure: Comparison with dobutamine

Rademaker, Miriam T.; Ellmers, Leigh J.; Charles, Christopher J.; Richards, A. Mark

doi:10.1016/j.ijcard.2015.06.011

Cited by 15 publications

(15 citation statements)

References 52 publications

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“…Consistent with our findings, these molecular reactions affect equally the damaged tissue in risk zone and the preserved tissue in remote zone, eliciting considerable heart adverse remodeling. Importantly, rats’ infusion with Ucn-2 prevented fibrosis in both areas in agreement with previous studies which showed that Ucn-2 decreased collagen deposition in the heart and suppressed the expression of fibrosis’ markers as TGF-β1 and collagen-1 ( Rademaker et al, 2015 ). In contrast, Ucn-2 didn’t inhibit I/R-induced cardiac hypertrophy.…”

Section: Discussionsupporting

confidence: 91%

Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

et al. 2018

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Aims: Urocortin-2 (Ucn-2) is a potent cardioprotector against Ischemia and Reperfusion (I/R) injuries. However, little is known about its role in the regulation of intracellular Ca2+ concentration ([Ca2+]i) under I/R. Here, we examined whether the addition of Ucn-2 in reperfusion promotes cardioprotection focusing on ([Ca2+]i handling.Methods and Results: Cardiac Wistar rat model of I/R was induced by transient ligation of the left coronary artery and experiments were conducted 1 week after surgery in tissue and adult cardiomyocytes isolated from risk and remote zones. We observed that I/R promoted significant alteration in cardiac contractility as well as an increase in hypertrophy and fibrosis in both zones. The study of confocal [Ca2+]i imaging in adult cardiomyocytes revealed that I/R decreased the amplitude of [Ca2+]i transient and cardiomyocytes contraction in risk and remote zones. Interestingly, intravenous infusion of Ucn-2 before heart’s reperfusion recovered significantly cardiac contractility and prevented fibrosis, but it didn’t affect cardiac hypertrophy. Moreover, Ucn-2 recovered the amplitude of [Ca2+]i transient and modulated the expression of several proteins related to [Ca2+]i homeostasis, such as TRPC5 and Orai1 channels. Using Neonatal Rat Ventricular Myocytes (NRVM) we demonstrated that Ucn-2 blunted I/R-induced Store Operated Ca2+ Entry (SOCE), decreased the expression of TRPC5 and Orai1 as well as their interaction in reperfusion.Conclusion: Our study provides the first evidences demonstrating that Ucn-2 addition at the onset of reperfusion attenuates I/R-induced adverse cardiac remodeling, involving the [Ca2+]i handling and inhibiting the expression and interaction between TRPC5 and Orai1.

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Section: Discussionsupporting

confidence: 91%

Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

et al. 2018

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“…Consistently, Ucn-1 stimulated caspase 3/7 and caspase 9, but not caspase 8 that is associated to death receptors-mediated apoptosis [ 27 ]. These data is contrary to Ucn-2 reduction of caspase 3 levels due to a significant induction of natriuresis and decreased tissue mediators of inflammation [ 10 , 28 ]. Ucn-1 stimulation of caspase 3/7 and 9 findings was supported with Ucn-1 regulation of apoptotic genes expression.…”

Section: Discussionmentioning

confidence: 89%

Urocortin-1 Mediated Cardioprotection Involves XIAP and CD40-Ligand Recovery: Role of EPAC2 and ERK1/2

et al. 2016

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AimsUrocortin-1 (Ucn-1) is an endogenous peptide that protects heart from ischemia and reperfusion (I/R) injuries. Ucn-1 is known to prevent cardiac cell death, but its role in the transcription of specific genes related to survival signaling pathway has not been fully defined. The aim of this study was to investigate the molecular signaling implicated in the improvement of cardiac myocytes survival induced by Ucn-1.Methods and ResultsUcn-1 administration before ischemia and at the onset of reperfusion, in rat hearts perfused in Langendorff system, fully recovered heart contractility and other hemodynamic parameters. Ucn-1 enhanced cell viability and decreased lactate dehydrogenase (LDH) release in adult cardiac myocytes subjected to simulated I/R. Annexin V-FITC/PI staining indicated that Ucn-1 promoted cell survival and decreased cell necrosis through Epac2 (exchange protein directly activated by cAMP) and ERK1/2 (extracellular signal–regulated kinases 1/2) activation. We determined that Ucn-1 shifted cell death from necrosis to apoptosis and activated caspases 9 and 3/7. Furthermore, mini-array, RT-qPCR and protein analyses of apoptotic genes showed that Ucn-1 upregulated the expression of CD40lg, Xiap and BAD in cells undergoing I/R, involving Epac2 and ERK1/2 activation.ConclusionsOur data indicate that Ucn-1 efficiently protected hearts from I/R damage by increasing the cell survival and stimulated apoptotic genes, CD40lg, Xiap and BAD, overexpression through the activation of Epac2 and ERK1/2.

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“…Recent studies in experimental HF have shown favourable effects of Ucn-2 treatment in pacing-induced HF, 13,14,32,33 myocardial infarction 15 and systemic hypertension. 24 Beneficial effects in healthy volunteers and patients with acute 17 and chronic HF 16,34 have further excited interest in the therapeutic potential of the urocortins, although whether or not the increased Ucn-2 circulating levels is a cardioprotective response is yet to be understood.…”

Section: Discussionmentioning

confidence: 99%

“…8 Additionally, the Ucn-2 necrosis and apoptosis 9,10 and decreasing infarct size in the rat heart after ischaemia-reperfusion injury. [10][11][12] Acute Ucn-2 administration in experimental heart failure (HF) has beneficial haemodynamic effects, while suppressing adverse neurohormonal responses, 13,14 whereas chronic treatment after experimental myocardial infarction improves cardiac function and structure. 15 In patients with stable congestive 16 and acute decompensated HF, 17 intravenous Ucn-2 produces an increase in cardiac output (CO) and left ventricular (LV) ejection fraction (EF) in association with a reduction in systemic vascular resistance, blood pressure and cardiac work.…”

Section: Introductionmentioning

confidence: 99%

Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension

Adão

Mendes-Ferreira

Santos‐Ribeiro

et al. 2018

Cardiovascular Research

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Urocortin 2 protects heart and kidney structure and function in an ovine model of acute decompensated heart failure: Comparison with dobutamine

Cited by 15 publications

References 52 publications

Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

Urocortin-1 Mediated Cardioprotection Involves XIAP and CD40-Ligand Recovery: Role of EPAC2 and ERK1/2

Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension

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