Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation Possibly by Akt and Erk1/2 Pathways

Huang, Shian; Zhu, Xiaoyun; Huang, Wenjun; He, Yuan; Pang, Lingpin; Lan, Xiaozhong; Shui, Xiaorong; Chen, Yanfang; Chen, Can; Lei, Wei

doi:10.1155/2017/6147294

Cited by 15 publications

(11 citation statements)

References 43 publications

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“…Increasing evidence has demonstrated that the Akt/mTOR signaling pathway is activated and involved in PAH via vasoconstriction and remodeling (47). Furthermore, blocking the Akt/mTOR signaling pathway reverses PAH in animal models (48,49). The present study indicated that SIRT1 upregulated Akt/mTOR in endothelial cells under hypoxic conditions.…”

Section: Discussionsupporting

confidence: 54%

SIRT1 promotes pulmonary artery endothelial cell proliferation by targeting the Akt signaling pathway

Ruan

Yao

et al. 2020

Exp Ther Med

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Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive increase in pulmonary vascular resistance and obliterative pulmonary vascular remodeling; however, the pathogenesis of the disease is not completely understood. Sirtuin 1 (SIRT1) is a histone deacetylase involved in cell survival and metabolism. The present study explored the potential role of SIRT1 in human pulmonary arterial endothelial cells (HPAECs) under hypoxic conditions. In vitro HPAECs were cultured and exposed to hypoxic conditions. Subsequently, SIRT1 expression levels were measured via western blotting, the generation of reactive oxygen species (ROS) was evaluated, and the interaction between SIRT1 and Akt was assessed via reverse transcription-quantitative PCR and western blotting. In addition, the effects of SIRT1 on cell proliferation and apoptosis were also investigated. The results indicated that hypoxia induced SIRT1 expression in pulmonary arterial endothelial cells, which may be associated with ROS generation. SIRT1 expression activated the Akt signaling pathway, which increased the expression levels of Bcl-2 and hypoxia-inducible factor-1 in HPAECs. Moreover, SIRT1 promoted HPAEC proliferation and inhibited HPAEC apoptosis. ROS generation enhanced the SIRT1/Akt axis, which was essential for epithelial cell injury under hypoxic conditions. Therefore, blocking SIRT1 may reduce hypoxia-induced pathological damage in HPAECs.

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Section: Discussionsupporting

confidence: 54%

SIRT1 promotes pulmonary artery endothelial cell proliferation by targeting the Akt signaling pathway

Ruan

Yao

et al. 2020

Exp Ther Med

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“…Our group also demonstrated that quercetin exerted vasodilator effect in isolated pulmonary arteries, induced apoptosis and inhibited cell proliferation in PASMC [106]. The mechanism involved in the antiproliferative effects in both PASMC and endothelial cells seem to involve AKT [106,108,109], FOXO1-mTOR [110], and altered Bax/Bcl-2 ratio [108,111].…”

Section: Flavonoids and Other Polyphenolsmentioning

confidence: 75%

Impact of Nutrition on Pulmonary Arterial Hypertension

et al. 2020

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Pulmonary arterial hypertension (PAH) is characterized by sustained vasoconstriction, vascular remodeling, inflammation, and in situ thrombosis. Although there have been important advances in the knowledge of the pathophysiology of PAH, it remains a debilitating, limiting, and rapidly progressive disease. Vitamin D and iron deficiency are worldwide health problems of pandemic proportions. Notably, these nutritional alterations are largely more prevalent in PAH patients than in the general population and there are several pieces of evidence suggesting that they may trigger or aggravate disease progression. There are also several case reports associating scurvy, due to severe vitamin C deficiency, with PAH. Flavonoids such as quercetin, isoflavonoids such as genistein, and other dietary polyphenols including resveratrol slow the progression of the disease in animal models of PAH. Finally, the role of the gut microbiota and its interplay with the diet, host immune system, and energy metabolism is emerging in multiple cardiovascular diseases. The alteration of the gut microbiota has also been reported in animal models of PAH. It is thus possible that in the near future interventions targeting the nutritional status and the gut dysbiosis will improve the outcome of these patients.

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“…Many studies have reported the anti-PH effects of these compounds in vitro and in vivo. Studies demonstrate that quercetin can inhibit pulmonary arterial endothelial cell transdifferentiation into smooth muscle-like cells by regulating Akt and ERK1/2 pathways and enhance the autophagy of PASMCs induced by hypoxia through the FoxO1-SENS3-mTOR pathway [27,28]. Quercetin can also interfere with the IRE1α-XBP1 pathway and TrkA/kt pathway, leading to reduced PASMC migration and cell cycle arrest, which in turn ameliorates hypoxia-induced PH [29,30].…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effects and Mechanism of Buyang Huanwu Decoction on Pulmonary Vascular Remodeling: Network and Experimental Analyses

Chen

Cui

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Pulmonary hypertension (PH) is a severe and progressive cardiovascular disease. Its pathological mechanism is complex, and the common pathological feature is pulmonary vascular remodeling. The efficacy of existing therapeutic agents is limited. Traditional Chinese medicine (TCM) has its unique advantages in the prevention and treatment of complex diseases. In this study, the approaches of network pharmacology combined with biological verification are employed to explore the role of Buyang huanwu decoction (BYHWD) in the treatment of PH. The active ingredients in BYHWD were first screened based on the ADME properties of the compounds. In turn, the mean of data mining was utilized to analyze the potential targets of BYHWD for the treatment of PH. On this basis, a series of interaction networks were constructed for searching the core targets. The genes including AKT1, MMP9, NOS3/eNOS, and EGFR were found to be possible key targets in BYHWD. The results of enrichment analysis showed that the targets of BYHWD focused on smooth muscle cell proliferation, migration, and apoptosis, which are classic biological processes involved in pulmonary vascular remodeling and are closely related to the PI3K-Akt-eNOS pathway. The methods of biological experiments were adopted to verify the above results. The present study elucidated the mechanism of BYHWD in the treatment of PH and provided new ideas for the clinical use of TCM in the treatment of PH.

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Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation Possibly by Akt and Erk1/2 Pathways

Cited by 15 publications

References 43 publications

SIRT1 promotes pulmonary artery endothelial cell proliferation by targeting the Akt signaling pathway

SIRT1 promotes pulmonary artery endothelial cell proliferation by targeting the Akt signaling pathway

Impact of Nutrition on Pulmonary Arterial Hypertension

Ameliorative Effects and Mechanism of Buyang Huanwu Decoction on Pulmonary Vascular Remodeling: Network and Experimental Analyses

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