Urocortin 2 in cardiovascular health and disease

Adão, Rui; Santos‐Ribeiro, Diana; Rademaker, Miriam T.; Leite‐Moreira, Adelino F.; Brás-Silva, Carmen

doi:10.1016/j.drudis.2015.02.012

Cited by 24 publications

(22 citation statements)

References 70 publications

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“…Our study demonstrated that Crhr2 protein is abundantly expressed in the human heart, and plasma Ucn2 levels were higher in patients with heart failure compared to healthy controls, indicating that endogenous Crhr2 is associated with heart failure in humans. Our findings are supported by clinical trials in heart failure that reported increased plasma Ucn2 was associated with heart failure (Davis et al, 2007a,b; Adão et al, 2015).…”

Section: Resultssupporting

confidence: 86%

“…The Crh peptide family activates the PKA, CaMKII, and AKT signaling pathways to temporarily increase cardiac function (Adão et al, 2015), but the effects of chronic activation of these pathways in the heart remains controversial. Preclinical studies showed that acute Crhr2 agonist infusion increases cardiac output by decreasing SBP (Chan et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

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Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction

Tsuda

Takefuji

Wettschureck

et al. 2017

Journal of Experimental Medicine

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction

Tsuda

Takefuji

Wettschureck

et al. 2017

Journal of Experimental Medicine

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“…The increase in cAMP concentration activates protein kinase A after urocortin treatment and also facilitates ERK phosphorylation [15, 35, 36]. This pathway activates the pro-survival Bcl-2 family and prevents the mitochondria permeability transition opening and apoptosis [37]. Another pathway activated upon urocortin treatment is the phosphoinositide 3-kinase (PI3K) pathway through the recruitment of the G-protein in corticotrophin-releasing factor receptor type 2 (CRFR2).…”

Section: Discussionmentioning

confidence: 99%

“…As a result, the downstream protein kinase B (Akt) is phosphorylated and activated [28, 38]. Activation of Akt leads to the sequestration of the pro-apoptotic protein BAD in the cytosol, which reduces the levels of free BAX and inhibits the further activation of apoptotic pathways [37]. Interaction of Akt and STAT-3 pathways can reduce myocardial damage and can play important roles in improving mitochondria functions in post-cardiac arrest myocardial dysfunction [39, 40].…”

Section: Discussionmentioning

confidence: 99%

Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction

et al. 2016

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AimsHemodynamic instability occurs following cardiac arrest and is associated with high mortality during the post-cardiac period. Urocortin is a novel peptide and a member of the corticotrophin-releasing factor family. Urocortin has the potential to improve acute cardiac dysfunction, as well as to reduce the myocardial damage sustained after ischemia reperfusion injury. The effects of urocortin in post-cardiac arrest myocardial dysfunction remain unclear.Methods and ResultsWe developed a preclinical cardiac arrest model and investigated the effects of urocortin. After cardiac arrest induced by 6.5 min asphyxia, male Wistar rats were resuscitated and randomized to either the urocortin treatment group or the control group. Urocortin (10 μg/kg) was administrated intravenously upon onset of resuscitation in the experimental group. The rate of return of spontaneous circulation (ROSC) was similar between the urocortin group (76%) and the control group (72%) after resuscitation. The left ventricular systolic (dP/dt40) and diastolic (maximal negative dP/dt) functions, and cardiac output, were ameliorated within 4 h after ROSC in the urocortin-treated group compared to the control group (P<0.01). The neurological function of surviving animals was better at 6 h after ROSC in the urocortin-treated group (p = 0.023). The 72-h survival rate was greater in the urocortin-treated group compared to the control group (p = 0.044 by log-rank test). Cardiomyocyte apoptosis was lower in the urocortin-treated group (39.9±8.6 vs. 17.5±4.6% of TUNEL positive nuclei, P<0.05) with significantly increased Akt, ERK and STAT-3 activation and phosphorylation in the myocardium (P<0.05).ConclusionsUrocortin treatment can improve acute hemodynamic instability as well as reducing myocardial damage in post-cardiac arrest myocardial dysfunction.

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“…Interestingly, however, the relationships among the different CRF ligands and their receptors, and the robust expression of CRFBP in the zebrafish heart, suggest that the relative contribution of the various cardiac CRF system components differs significantly between fish and mammals. Beyond its cytoprotective functions, the cardiac CRF system also mediates hemodynamic and bioenergetic effects that enhance cardiovascular function and promotes recovery from ischemia/reoxygenation exposure (1,57). For example, administration of urocortins in mammals potently elevates cardiac contractility and output, improves coronary blood flow, and preserves the high-energy phosphate stores of the heart (10,59,68,72,79).…”

Section: Perspectives and Significancementioning

confidence: 99%

CRF and urocortin 3 protect the heart from hypoxia/reoxygenation-induced apoptosis in zebrafish

Williams

Bergstrome

Scott

et al. 2017

American Journal of Physiology-Regulatory, Integrative and Comp

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Fish routinely experience environmental hypoxia and have evolved various strategies to tolerate this challenge. Given the key role of the CRF system in coordinating the response to stressors and its cardioprotective actions against ischemia in mammals, we sought to characterize the cardiac CRF system in zebrafish and its role in hypoxia tolerance. We established that all genes of the CRF system, the ligands CRFa, CRFb, urotensin 1 (UTS1), and urocortin 3 (UCN3); the two receptor subtypes (CRFR1 and CRFR2); and the binding protein (CRFBP) are expressed in the heart of zebrafish: > > > > > In vivo, exposure to 5% O saturation for 15 min and 90 min of recovery resulted in four- to five-fold increases in whole heart and mRNA levels but did not affect the gene expression of other CRF system components. In vitro, as assessed by monitoring caspase 3 activity and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells, pretreatment of excised whole hearts with CRF or UCN3 for 30 min prevented the increase in apoptosis associated with exposure to 1% O saturation for 30 min with a 24-h recovery. Lastly, the addition of the nonselective CRF receptor antagonist αh-CRF prevented the cytoprotective effects of CRF. We show that the CRF system is expressed in fish heart, is upregulated by hypoxia, and is cytoprotective. These findings identify a novel role for the CRF system in fish and a new strategy to tolerate hypoxia.

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Urocortin 2 in cardiovascular health and disease

Cited by 24 publications

References 70 publications

Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction

Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction

Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction

CRF and urocortin 3 protect the heart from hypoxia/reoxygenation-induced apoptosis in zebrafish

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