Oxidative and nitrosative signalling in pulmonary arterial hypertension — Implications for development of novel therapies

Hansen, Thomas; Galougahi, Keyvan Karimi; Celermajer, David S.; Rasko, Nathalie; Tang, Owen; Bubb, Kristen J.; Figtree, Gemma A.

doi:10.1016/j.pharmthera.2016.05.005

Cited by 41 publications

(29 citation statements)

References 162 publications

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“…Oxidative tissue injury participates in the pathogenesis of chronic hypoxic pulmonary hypertension (HPH) [741] , [742] . HPH is caused by persistent lung hypoxia.…”

Section: The Emerging Roles Of Redox Network In Tumor Cell Proliferamentioning

confidence: 99%

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

et al. 2017

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The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

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“…Oxidative tissue injury participates in the pathogenesis of chronic hypoxic pulmonary hypertension (HPH) [741] , [742] . HPH is caused by persistent lung hypoxia.…”

Section: The Emerging Roles Of Redox Network In Tumor Cell Proliferamentioning

confidence: 99%

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

et al. 2017

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“…Currently, multiple antioxidants and small molecules have also been identified as having beneficial effects against the deleterious effects of PAH in different experimental models [13-16]. Gene manipulation research has also confirmed the effects of antioxidants, which can be applied in prevention strategies against PAH.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Jia

et al. 2017

Cell Physiol Biochem

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Background/Objectives: The polyphenol resveratrol (Rev) has been found to exhibit various beneficial effects including prevention of pulmonary arterial hypertension (PAH). The present study was designed to investigate the action and potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells (PASMCs). Methods: PAH rats were established by exposure to hypoxia for 21 days. Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then treated with Rev or SRT1720 in vitro. Western blot was performed to detect the protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out to verify cell proliferation. In addition, the TUNEL positive assay and flow cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability transition (mPT) was identified by confocal microscopy. Right ventricular systolic pressure (RVSP) was determined with a Gould pressure transducer, and right ventricular hypertrophy (RVH) was determined by weighing the cardiac muscle. Results: We demonstrated that Rev could reverse the remodelling of the pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down-regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious effect on the protein expression of SIRT1. In addition, Rev could induce mitochondrial swelling and nuclear pyknosis, leading to small, dense, and dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720, a specific activator of SIRT1, significantly retarded PASMC proliferation and promoted PASMC apoptosis in vitro. The mechanism could be associated with inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and reduced RVH. Conclusion: Rev produced a beneficial effect partially by enhancing the activation of SIRT1, thus improving RVSP and reducing RVH. SIRT1 activation increased PASMC apoptosis by inducing mPT dysfunction, which might be a novel future strategy for the treatment of PAH.

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“…ROS are generated during metabolic process of the cells, if it is unchecked by antioxidant defense system, cell will incline toward oxidative stress (Alcala et al, ; Lubos, Loscalzo, & Hand, ; Mortezaee & Khanlarkhani, ). In few conditions ROS could react with nitric oxide and generate higher reactive nitrogen species (RNS) known as peroxy nitrite (Chance, Sies, & Boveris, ; Hansen et al, ; Liochev & Fridovich, ). Increase in serum TBARS and nitrite/nitrate in steatosis (group 2) animals proves contributions of ROS and RNS in the development of NASH (group 3).…”

Section: Discussionmentioning

confidence: 99%

Protective role of germinated mung bean against progression of non-alcoholic steatohepatitis in rats: A dietary therapy to improve fatty liver health

2018

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The current research was focused at investigating the different doses of germinated mung bean (GMB) (Vigna Radiata [Fabaceae]) on progression of non‐alcoholic steatohepatitis (NASH) from steatosis. Beneficial effects of GBM against NASH from steatosis‐induced liver injury were apparent from decreased serum transaminase activities, lipid peroxidation and nitrite/nitrate contents, and recoupment of glutathione. Enzymatic antioxidants were inclined toward normal in high dose GMB supplemented rats. On the other hand low dose of GMB prevented further alteration when compared with steatosis. Gene expression analysis shows that supplementation of GMB restores the antioxidant enzyme gene expressions. GMB effect was confirmed through histopathological observation, which is correlated along with lipid reduction and various inflammatory cytokine restoration. Further GMB could abrogate alleviated mitochondrial ROS generation. In summary, GMB has a huge potential to decrease the consequence of oxidative stress, which could be one of the contributing mechanism to its protective effect in attenuating the progression of NASH. Practical applications Mung bean is widely consumed world‐wide by all the population. Germinated mung bean prevents development of steatohepatitis from steatosis. Higher consummation may be recommended for their betterment of liver health.

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Oxidative and nitrosative signalling in pulmonary arterial hypertension — Implications for development of novel therapies

Cited by 41 publications

References 162 publications

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Protective role of germinated mung bean against progression of non-alcoholic steatohepatitis in rats: A dietary therapy to improve fatty liver health

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