MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/nitrative stress and subsequent dysfunction in the heart

Varga, Zoltán V.; Kupai, Krisztina; Szűcs, Gergő; Gáspár, Renáta; Pálóczi, János; Faragó, Nóra; Zvara, Ágnes; Puskás, László G.; Rázga, Zsolt; Tiszlavicz, László; Bencsik, Péter; Görbe, Anikó; Csonka, Csaba; Ferdinándy, Péter; Csont, Tamás

doi:10.1016/j.yjmcc.2013.05.009

Cited by 162 publications

(150 citation statements)

References 57 publications

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“…Superoxide anion (O2 − ) is a reactive oxygen radical that reacts with NO to form peroxynitrite. The in situ fluorescent dihydroethidium staining was performed to evaluate intracellular production of superoxide anion (Varga et al, 2013). Unfixed frozen heart sections (30 μm) were placed on glass slides and incubated in 10 −6 mol·L −1 dihydroethidium (Sigma, St. Louis, MO, USA) in PBS buffer (pH 7.4) at 37°C for 30 min in a dark humidified container.…”

Section: Experimental Design 2: Investigating the Role Of Peroxynitrimentioning

confidence: 99%

Rapid ventricular pacing‐induced postconditioning attenuates reperfusion injury: effects on peroxynitrite, RISK and SAFE pathways

Pipicz

Varga

Kupai

et al. 2015

British J Pharmacology

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Background and PurposeRapid ventricular pacing (RVP) applied before an index ischaemia has anti‐ischaemic effects. Here, we investigated whether RVP applied after index ischaemia attenuates reperfusion injury and whether peroxynitrite, reperfusion injury salvage kinase (RISK) and survival activating factor enhancement (SAFE) pathways as well as haem oxygenase 1 (HO1) are involved in the mechanism of RVP‐induced postconditioning.Experimental ApproachLangendorff perfused rat hearts were subjected to 30 min regional ischaemia and 120 min reperfusion with or without ischaemic postconditioning (6 × 10/10 s reperfusion/ischaemia; IPost) or RVP (6 × 10/10 s non‐pacing/rapid pacing at 600 bpm) applied at the onset of reperfusion.Key ResultsMeta‐analysis of our previous studies revealed an association between longer reperfusion‐induced ventricular tachycardia/fibrillation with decreased infarct size. In the present experiments, we tested whether RVP is cardioprotective and found that both IPost and RVP significantly decreased infarct size; however, only RVP attenuated the incidence of reperfusion‐induced ventricular tachycardia. Both postconditioning methods increased the formation of cardiac 3‐nitrotyrosine and superoxide, and non‐significantly enhanced Akt phosphorylation at the beginning of reperfusion without affecting ERK1/2 and STAT3, while IPost alone induced HO1. Application of brief ischaemia/reperfusion cycles or RVP without preceding index ischaemia also facilitated peroxynitrite formation; nevertheless, only brief RVP increased STAT3 phosphorylation.Conclusions and ImplicationsShort periods of RVP at the onset of reperfusion are cardioprotective and increase peroxynitrite formation similarly to IPost and thus may serve as an alternative postconditioning method. However, downstream mechanisms of the protection elicited by IPost and RVP seem to be partially different.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

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Section: Experimental Design 2: Investigating the Role Of Peroxynitrimentioning

confidence: 99%

Rapid ventricular pacing‐induced postconditioning attenuates reperfusion injury: effects on peroxynitrite, RISK and SAFE pathways

Pipicz

Varga

Kupai

et al. 2015

British J Pharmacology

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“…In agreement with previous results, we found markedly decreased global (systolic and diastolic) cardiac function in our EAM model. The inflammation-driven necrosis, loss of functional myocytes and oxidative/ nitrative stress-induced contractile protein damage can play a crucial role in the development of systolic dysfunction (48,49). We observed significant deterioration of the systolic performance derived from classic load-dependent (ejection fraction, cardiac output and dP/dt max ) and load-independent (ESPVR, PRSW) functional parameters.…”

Section: Discussionmentioning

confidence: 79%

Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

Lee

Erdélyi

Mátyás

et al. 2016

Mol Med

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“…Nox isoform presented in VSMCs is the potential target for miR‐146a, while the isoform expressed in ECs and leucocytes remains unaffected 27, 53, 54. Increased expression of Nox in ECs leads consequently to oxidative/nitrosative stress in the heart 54.…”

Section: Mirna Signatures Related To Pathological Inflammatory Conditmentioning

confidence: 99%

“…Increased expression of Nox in ECs leads consequently to oxidative/nitrosative stress in the heart 54. However, miR‐146a and 181s which induce expression of inflammatory mediators IRAK‐1 and TNF receptor‐associated factor‐6 are also up‐regulated in ageing cells 28.…”

Section: Mirna Signatures Related To Pathological Inflammatory Conditmentioning

confidence: 99%

MicroRNAs; easy and potent targets in optimizing therapeutic methods in reparative angiogenesis

Pourrajab

Zarch

Hekmatimoghaddam

et al. 2015

J Cellular Molecular Medi

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The age‐related senescence of adult tissues is associated with the decreased level of angiogenic capability and with the development of a degenerative disease such as atherosclerosis which thereafter result in the deteriorating function of multiple systems. Findings indicate that tissue senescence not only diminishes repair processes but also promotes atherogenesis, serving as a double‐edged sword in the development and prognosis of ischaemia‐associated diseases. Evidence evokes microRNAs (miRNAs) as molecular switchers that underlie cellular events in different tissues. Here, miRNAs would promote new potential targets for optimizing therapeutic methods in blood flow recovery to the ischaemic area. Effectively beginning an ischaemia therapy, a more characteristic of miRNA changes in adult tissues is prerequisite and in the forefront. It may also be a preliminary phase in treatment strategies by stem cell‐based therapy.

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MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/nitrative stress and subsequent dysfunction in the heart

Cited by 162 publications

References 57 publications

Rapid ventricular pacing‐induced postconditioning attenuates reperfusion injury: effects on peroxynitrite, RISK and SAFE pathways

Rapid ventricular pacing‐induced postconditioning attenuates reperfusion injury: effects on peroxynitrite, RISK and SAFE pathways

Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

MicroRNAs; easy and potent targets in optimizing therapeutic methods in reparative angiogenesis

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