TRPV1 agonism inhibits endothelial cell inflammation via activation of eNOS/NO pathway

Wang, Youping; Chen, Lin; Xu, Hui; Liu, Suxiao; Zhu, Fei-yun; Yan, Fengna; Shen, Si; Zhu, Min

doi:10.1016/j.atherosclerosis.2017.03.016

Cited by 72 publications

(67 citation statements)

References 33 publications

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“…57 On the other hand, PI3K/AKT/eNOS pathway is an important signaling pathway for ER stress, ROS production, inflammation and apoptosis in endothelial cells. [61][62][63][64] LY294002 had no effects on the functions of the HUVECs, which is consistent with previous findings. 65 We are speculating that the PI3K/AKT/eNOS signaling is activated by detrimental/protective stimulus, which can be effectively inhibited by LY294002; while at normal conditions, the PI3K/ATK/eNOS signaling may not be activated.…”

Section: Dovepresssupporting

confidence: 92%

<p>Hydrogen Sulfide Protects Against High Glucose-Induced Human Umbilical Vein Endothelial Cell Injury Through Activating PI3K/Akt/eNOS Pathway</p>

Lin

Yang

Wei

et al. 2020

DDDT

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Dysfunction of endothelial cells plays a key role in the pathogenesis of diabetic atherosclerosis. High glucose (HG) has been found as a key factor in the progression of diabetic complications, including atherosclerosis. PI3K/Akt/eNOS signaling pathway has been shown to involve in HG-induced vascular injuries. Hydrogen sulfide (H 2 S) has been found to exhibit protective effects on HG-induced vascular injuries. Moreover, H 2 S activates PI3K/Akt/eNOS pathway in endothelial cells. Thus, the present study aimed to determine if H 2 S exerts protective effects against HG-induced injuries of human umbilical vein endothelial cells (HUVECs) via activating PI3K/Akt/eNOS signaling. Materials and Methods: The endothelial protective effects of H 2 S were evaluated and compared to the controlled groups. Cell viability, cell migration and tube formation were determined by in vitro functional assays; protein levels were evaluated by Western blot assay and ELISA; cell apoptosis was determined by Hoechst 33258 nuclear staining; Reactive oxygen species (ROS) production was evaluated by the ROS detection kit. Results: HG treatment significantly inhibited PI3K/Akt/eNOS signaling in HUVECs, which was partially reversed by the H2S treatment. HG treatment inhibited cell viability of HUVECs, which were markedly prevented by H 2 S or PI3K agonist Y-P 740. HG treatment also induced HUVEC cell apoptosis by increasing the protein levels of cleaved caspase 3, Bax and Bcl-2, which were significantly attenuated by H 2 S or 740 Y-P. ROS production and gp91 phox protein level were increased by HG treatment in HUVECs and this effect can be blocked by the treatment with H 2 S or Y-P 740. Moreover, HG treatment increased the protein levels of pro-inflammatory cytokines, caspase-1 and phosphorylated JNK, which was significantly attenuated by H 2 S or Y-P 740. Importantly, the cytoprotective effect of H 2 S against HG-induced injury was inhibited by LY294002 (an inhibitor of PI3K/Akt/eNOS signaling pathway). Conclusion: The present study demonstrated that exogenous H 2 S protects endothelial cells against HG-induced injuries by activating PI3K/Akt/eNOS pathway. Based on the above findings, we proposed that reduced endogenous H 2 S levels and the subsequent PI3K/Akt/ eNOS signaling impairment may be the important pathophysiological mechanism underlying hyperglycemia-induced vascular injuries.

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Section: Dovepresssupporting

confidence: 92%

<p>Hydrogen Sulfide Protects Against High Glucose-Induced Human Umbilical Vein Endothelial Cell Injury Through Activating PI3K/Akt/eNOS Pathway</p>

Lin

Yang

Wei

et al. 2020

DDDT

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“…Wang et al demonstrated that activating TRPV1 in endothelial cells could exert an antiinflammatory function characterized by a decrease in proinflammatory cytokine/chemokine production and adhesion molecule expression, as well as monocyte adhesion. This function may be due to the downregulation of NF-kB, a transcription factor modulating proinflammatory factor expression, by activation of TRPV1 via the Ca 2+ /PI3K/Akt/eNOS/ NO pathway [79]. The anti-inflammatory role of TRPV1 is also found in dendritic cells (DCs), a kind of immune cell presenting antigens to T cells and producing different cytokines to participate in immune-inflammatory responses.…”

Section: Trpv1 In Inflammatory Cellsmentioning

confidence: 99%

“…Regardless of how complicated the role of TRPV1 is in inflammation, the effects of TRPV1 directly on inflammatory cells and indirectly on inflammatory cells through these three neuropeptides seem to all involve NF-kB, a transcription factor associated with proinflammatory factors, such as TNF-α, IL-6, MCP-1, ICAM-1, and VCAM-1. The proinflammatory effects are mediated by their upregulation of NF-kB, whereas the anti-inflammatory roles are due to their downregulation of NF-kB [59,66,75,79]. However, a large number of studies are necessary to detail the role of the TRPV1/NF-kB signaling pathway in inflammation, especially in the progression of PAH.…”

Section: Trpv1 In Inflammatory Cellsmentioning

confidence: 99%

The potential role of TRPV1 in pulmonary hypertension: Angel or demon?

Zhang

Huang

et al. 2019

Channels

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Pulmonary hypertension (PH) is a pathological state defined by increased pulmonary artery pressure, the pathogenesis of which is related to genetic mutations, intracellular calcium ([Ca 2+ ] i), inflammation and proliferation. Transient receptor potential vanilloid subfamily member 1 (TRPV1) is a nonselective cation channel expressed in neural and nonneural cells, including pulmonary vessels and nerves. As a calcium channel, TRPV1 can make vessels contracted, and promote smooth muscle cells proliferation through calcium-dependent transcription factors. Activation of TRPV1 in sensory nerves can release neuropeptides, including calcitonin generelated peptide (CGRP), substance P (SP), and somatostatin (SST), which can regulate inflammation via transcription factor NF-kB. Considering the increased level of [Ca 2+ ] i and inflammation in the pathogenesis of PH, our review summarizes the role of TRPV1 in PH with regard to [Ca 2+ ] i , neuropeptides, and inflammation. In view of the limited research illustrating the relationship between TRPV1 and PH directly, our review also considers the role of TRPV1 in other types of vascular inflammation. Through this review, we hope to raise awareness about the function of TRPV1 in PH.

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“…Nonivamide (pelargonic acid vanillylamide [PAVA]; C 17 H 27 NO 3 ), the phytochemical that is naturally found in hot peppers and oleoresin capsicum (Reilly, Crouch, Yost, & Fatah, 2002), is a less pungent capsaicin analogue that is similar to capsaicin in regard to chemical structure and pharmacological effects (Fang, Leu, Wang, & Tsai, 2002). PAVA is a transient receptor potential vanilloid 1 (TRPV1) agonist (Haas et al, 1997); the activation of TRPV1, which results in the suppression of the inflammatory response, also modulates metabolic pathways that improve cardiovascular health (Medina-Contreras et al, 2017;Wang et al, 2017). Moreover, PAVA has been shown to exert anti-obesity and antioxidant effects in addition to pain relief (Morales-Martínez et al, 2016;Srinivasan, 2016).…”

mentioning

confidence: 99%

Synergistic effects of the capsaicinoid nonivamide and rosuvastatin on obesity‐related endothelial dysfunction in rat fed a high‐fat diet

Sivasinprasasn

Wikan

Tocharus

et al. 2019

Phytotherapy Research

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Capsaicinoid nonivamide (PAVA) and rosuvastatin (RSV) have been shown to exert antioxidant and anti‐obesity effects in various animal models, but it is unknown whether their combination would be an effective treatment for obesity‐related endothelial dysfunction. This study aimed to investigate the mechanism of PAVA in synergy with RSV. Male Sprague–Dawley rats were given a high‐fat diet (HFD) or normal diet during a 20‐week period. At 16 weeks, rats in each diet group were divided into subgroups. Normal diet rats were divided into Normal diet control, Normal diet with PAVA, and Normal diet with RSV groups. HFD rats were subdivided into HFD control, HFD with PAVA, HFD with RSV, and HFD with PAVA + RSV groups and evaluated for metabolic parameters, blood pressure, aortic function, and histological change of the aorta in rats. Our results showed the combined therapy had a significantly greater effect than the monotherapy in all measured parameters; this was indicated by improvement in insulin sensitivity and aortic function, decreased blood pressure, lower oxidative stress, and prevention of vascular damage. The synergistic effect of the PAVA and RSV can protect HFD‐induced obesity‐related endothelial dysfunction, suggesting that the combination of PAVA and RSV could be an effective alternative treatment for obesity‐related complications in patients with cardiovascular disease.

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TRPV1 agonism inhibits endothelial cell inflammation via activation of eNOS/NO pathway

Cited by 72 publications

References 33 publications

<p>Hydrogen Sulfide Protects Against High Glucose-Induced Human Umbilical Vein Endothelial Cell Injury Through Activating PI3K/Akt/eNOS Pathway</p>

<p>Hydrogen Sulfide Protects Against High Glucose-Induced Human Umbilical Vein Endothelial Cell Injury Through Activating PI3K/Akt/eNOS Pathway</p>

The potential role of TRPV1 in pulmonary hypertension: Angel or demon?

Synergistic effects of the capsaicinoid nonivamide and rosuvastatin on obesity‐related endothelial dysfunction in rat fed a high‐fat diet

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