Molecular mechanisms underlying oxytocin-induced cardiomyocyte protection from simulated ischemia–reperfusion

Gonzalez-Reyes, Araceli; Ménaouar, Ahmed; Yip, Denis; Danalache, Bogdan; Plante, Eric; Noiseux, Nicolas; Gutkowska, Jolanta; Jankowski, Marek

doi:10.1016/j.mce.2015.04.028

Cited by 56 publications

(61 citation statements)

References 50 publications

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“…Most of the up-to-date studies on the role of oxytocin in myocardial infarction were based on experimental methods involving an ischaemia-reperfusion model in vitro [19, 26, 27] or in vivo [16, 17]. In the study by Jankowski et al, myocardial infarction was evoked by chronic ligation of the left anterior descending coronary artery [17].…”

Section: Resultsmentioning

confidence: 99%

“…The authors of that study did not measure oxytocin mRNA expression and protein level at the same time; thus, it cannot be excluded that endogenous intracardiac OT could be partially responsible for the observed cardioprotective effects. In the other study, pretreatment with OT before ischaemia-reperfusion exposure resulted in the reduction of infarct size and activation of the prosurvival p38-MAPK and Akt-kinase pathways [26, 27]. In the in vitro model of ischaemia-reperfusion-induced myocardial damage, Ondrejcakova et al showed that exposure to OT prior to ischaemia resulted in the reduction of the infarct size due to the negative chronotropic effect [19].…”

Section: Resultsmentioning

confidence: 99%

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Increased Activity of the Intracardiac Oxytocinergic System in the Development of Postinfarction Heart Failure

Wsol

Kasarełło

Kuch

et al. 2016

BioMed Research International

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Aim. The present study was designed to test the hypothesis that the development of postinfarction heart failure is associated with a change of activity of the intracardiac oxytocinergic system. Methods. Experiments were performed on male Sprague-Dawley rats subjected to myocardial infarction or sham surgery. Four weeks after the surgery, blood samples were collected and the samples of the left ventricle (LV) and right ventricle (RV) were harvested for evaluation of the mRNA expression (RT-PCR) of oxytocin (OT), oxytocin receptor (OTR), natriuretic peptides, and the level of OT and OTR protein (ELISA). The concentration of N-terminal B-type natriuretic peptide was measured to determine the presence of heart failure. Results. Plasma NT-proBNP concentration was higher in the infarcted rats. In the infarcted rats, the expression of OT mRNA and the OT protein level were higher in the RV. There were no significant differences between infarcted and noninfarcted rats in the expression of OT mRNA and in the OT protein level in the fragments of the LV. In both the left and the right ventricles, OTR mRNA expression was lower but the level of OTR protein was higher in the infarcted rats. Conclusions. In the present study, we indicate that postinfarction heart failure is associated with an increased activity of the intracardiac oxytocinergic system.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Increased Activity of the Intracardiac Oxytocinergic System in the Development of Postinfarction Heart Failure

Wsol

Kasarełło

Kuch

et al. 2016

BioMed Research International

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“…However, Rimoldi et al reported that stimulation of OTR with OT is associated with EGFR transactivation and ERK activation in HEK293 cells, resulting in opposite effects on cell growth [ 43 ]. And treatment with OT prevented the lethal reperfusion injury of H9c2 cardiomyoblasts and increased ERK phosphorylation [ 44 ]. It is important to mention that administration of OT in vivo effectively improved autism spectrum disorder-like symptoms, associated with inhibited phosphorylation of ERK in lesioned medial amygdalae [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice

Yuan

Liu

Bai

et al. 2016

J Neuroinflammation

160

139

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BackgroundOveractivated microglia is involved in various kinds of neurodegenerative diseases. Suppression of microglial overactivation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory effects of oxytocin (OT), which is a highly conserved nonapeptide with hormone and neurotransmitter properties, were investigated in vitro and in vivo.MethodsBV-2 cells and primary microglia were pre-treated with OT (0.1, 1, and 10 μM) for 2 h followed by LPS treatment (500 ng/ml); microglial activation and pro-inflammatory mediators were measured by Western blot, RT-PCR, and immunofluorescence. The MAPK and NF-κB pathway proteins were assessed by Western blot. The intracellular calcium concentration ([Ca2+]i) was determined using Fluo2-/AM assay. Intranasal application of OT was pre-treated in BALB/C mice (adult male) followed by injected intraperitoneally with LPS (5 mg/kg). The effect of OT on LPS-induced microglial activation and pro-inflammatory mediators was measured by Western blot, RT-PCR, and immunofluorescence in vivo.ResultsUsing the BV-2 microglial cell line and primary microglia, we found that OT pre-treatment significantly inhibited LPS-induced microglial activation and reduced subsequent release of pro-inflammatory factors. In addition, OT inhibited phosphorylation of ERK and p38 but not JNK MAPK in LPS-induced microglia. OT remarkably reduced the elevation of [Ca2+]i in LPS-stimulated BV-2 cells. Furthermore, a systemic LPS-treated acute inflammation murine brain model was used to study the suppressive effects of OT against neuroinflammation in vivo. We found that pre-treatment with OT showed marked attenuation of microglial activation and pro-inflammatory factor levels.ConclusionsTaken together, the present study demonstrated that OT possesses anti-neuroinflammatory activity and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.

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“…To date, the expression of the OT in the heart was described only in normotensive rats [12,23,24]. However, in our previous study, we demonstrated increased expression of OT in the hearts of rats developing post-myocardial infarction heart failure [24], where this effect was potentially associated with the antifibrogenic, antihypertrophic, anti-inflammatory effect resulting in the reduction of myocardial damage [14,15,22]. In the study by Menaouar et al oxytocin and its precursor OT-Gly-Lys-Arg (OT-GKR) blocked endothelin-1-induced cardiac hypertrophy ex vivo by activating cGMP/protein kinase G pathway and the PI3K/Akt pathway, considered essential for physiological growth but also for inhibition of pathological hypertrophy in cardiomyocytes [16,25].…”

Section: Discussionmentioning

confidence: 74%

Increased oxytocinergic system activity in the cardiac muscle in spontaneously hypertensive SHR rats

et al. 2019

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Introduction: The present study aimed to determine whether the presence of cardiac hypertrophy due to arterial hypertension is associated with a change in the activity of the oxytocinergic system in cardiomyocytes. Material and methods: The experiments were performed on male, spontaneously hypertensive rats (SHR, n = 10) and normotensive Wistar-Kyoto rats (WKY, n = 12). Blood samples were collected from both SHR and WKY animals to asses plasma oxytocin (OT) concentration; the rats were sacrificed by decapitation. Samples of the left and right ventricles were harvested for the analysis of the OT and oxytocin receptor (OTR) protein by ELISA, and OT and OTR mRNA expression by RT-PCR. Immunohistopathological studies were performed to confirm the presence of OTR receptors in the cardiac muscle of the ventricles. Results: Plasma OT concentration did not differ between SHR and WKY rats. In the SHR rats, the expression of OT mRNA and the OT protein level was higher in the left and the right ventricle, while OTR mRNA expression was significantly lower in both the left and the right ventricle. However, the level of OTR protein was higher only in the left ventricle of the SHR rats. The presence of OTR receptors was confirmed by immunohistochemical analysis in the muscle of the right and left ventricle. Conclusions: The presence of arterial hypertension is associated with increased activity of the oxytocinergic system in the heart, especially in the area of the left ventricle. These findings support the important role of this system in the maintenance of cardiovascular homeostasis.

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Molecular mechanisms underlying oxytocin-induced cardiomyocyte protection from simulated ischemia–reperfusion

Cited by 56 publications

References 50 publications

Increased Activity of the Intracardiac Oxytocinergic System in the Development of Postinfarction Heart Failure

Increased Activity of the Intracardiac Oxytocinergic System in the Development of Postinfarction Heart Failure

Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice

Increased oxytocinergic system activity in the cardiac muscle in spontaneously hypertensive SHR rats

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