Celastrol Alleviates Aortic Valve Calcification Via Inhibition of NADPH Oxidase 2 in Valvular Interstitial Cells

Liu, Huibing; Wang, Libo; Pan, Yating; Wang, Xuehui; Ding, Yu‐An; Zhou, Chang; Shah, Ajay M.; Zhao, Guoan; Zhang, Min

doi:10.1016/j.jacbts.2019.10.004

Cited by 41 publications

(58 citation statements)

References 54 publications

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“…PKC activates Reactive oxygen species (ROS) generating NOX2 [34], and the NOX2 might be involve in vascular calcification [35,36]. Upregulated NOX2 induced increased expression of CBFα-1 and led to calcification of vascular interstitial cells [37]. AGE also activated TGFβ and BMP2, which in turn activated Smad signals and led to an increased expression of CBFα-1 [19].…”

Section: Discussionmentioning

confidence: 99%

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Attenuating Effects of Pyrogallol-Phloroglucinol-6,6-Bieckol on Vascular Smooth Muscle Cell Phenotype Changes to Osteoblastic Cells and Vascular Calcification Induced by High Fat Diet

Son

Jang³

et al. 2020

Nutrients

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Advanced glycation end products/receptor for AGEs (AGEs/RAGEs) or Toll like receptor 4 (TLR4) induce vascular smooth muscle cell (VSMC) phenotype changes in osteoblast-like cells and vascular calcification. We analyzed the effect of Ecklonia cava extract (ECE) or pyrogallol-phloroglucinol-6,6-bieckol (PPB) on VSMC phenotype changes and vascular calcification prompted by a high-fat diet (HFD). HFD unregulated RAGE, TLR4, transforming growth factor beta (TGFβ), bone morphogenetic protein 2 (BMP2), protein kinase C (PKC), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signals in the aorta of mice. ECE and PPB restored the increase of those signal pathways. AGE- or palmitate-treated VSMC indicated similar changes with the animal. HFD increased osteoblast-like VSMC, which was evaluated by measuring core-binding factor alpha-1 (CBFα-1) and osteocalcin expression and alkaline phosphatase (ALP) activity in the aorta. ECE and PPB reduced vascular calcification, which was analyzed by the calcium deposition ratio, and Alizarin red S stain was increased by HFD. PPB and ECE reduced systolic, diastolic, and mean blood pressure, which increased by HFD. PPB and ECE reduced the phenotype changes of VSMC to osteoblast-like cells and vascular calcification and therefore lowered the blood pressure.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Attenuating Effects of Pyrogallol-Phloroglucinol-6,6-Bieckol on Vascular Smooth Muscle Cell Phenotype Changes to Osteoblastic Cells and Vascular Calcification Induced by High Fat Diet

Son

Jang³

et al. 2020

Nutrients

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“…Meanwhile, the expression level of epithelial cell marker E-cadherin is decreased, the mesenchymal markers vimentin and α-SMA are both promoted, as evidenced by induced renal fibrosis generation 42 , 79 . Moreover, knockdown of endogenous Nox2 significantly activates GSK-3β by inhibiting its phosphorylation in a rabbit CAVD model, along with significant attenuation of aortic valve ROS production and fibrosis 80 . These findings reveal that ROS trigger GSK-3β inactivation in a manner dependent on Ser9 phosphorylation and subsequently activate the downstream signaling cascade to promote the process of fibrogenesis.…”

Section: Relationship Between Gsk-3β and Ros In Fibrosismentioning

confidence: 92%

“…These results suggest that GSK-3β activators may provide a novel therapeutic strategy for the treatment of myocardial fibrosis and heart failure. Additionally, celastrol, a natural compound and nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2) inhibitor, can mitigate aortic valve fibrosis by upregulating GSK-3β gene expression in cultured porcine aortic valvular interstitial cells (AVICs) and the rabbit calcific aortic valve disease (CAVD) models, as evidenced by attenuated fibrotic marker FN 80 .…”

Section: Roles Gsk-3β Plays In the Fibrosis Of Multiple Organsmentioning

confidence: 99%

Glycogen synthase kinase-3β: a promising candidate in the fight against fibrosis

et al. 2020

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Fibrosis exists in almost all organs/tissues of the human body, plays an important role in the occurrence and development of diseases and is also a hallmark of the aging process. However, there is no effective prevention or therapeutic method for fibrogenesis. As a serine/threonine (Ser/Thr)-protein kinase, glycogen synthase kinase-3β (GSK-3β) is a vital signaling mediator that participates in a variety of biological events and can inhibit extracellular matrix (ECM) accumulation and the epithelial-mesenchymal transition (EMT) process, thereby exerting its protective role against the fibrosis of various organs/tissues, including the heart, lung, liver, and kidney. Moreover, we further present the upstream regulators and downstream effectors of the GSK-3β pathway during fibrosis and comprehensively summarize the roles of GSK-3β in the regulation of fibrosis and provide several potential targets for research. Collectively, the information reviewed here highlights recent advances vital for experimental research and clinical development, illuminating the possibility of GSK-3β as a novel therapeutic target for the management of tissue fibrosis in the future.

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“…In addition to AA, its upstream PUFA DGLA alleviates atherosclerosis and aortic calcification after supplementation in apolipoprotein E deficient mice [65]. This was accompanied by a decreased mRNA expression of adhesion molecules ICAM-1, VCAM-1 and NADPH oxidase subunits, which have all previously been shown to contribute to aortic valve inflammation and oxidative stress driven calcification [21,27,66]. The observed beneficial effect could be the result of increased metabolism of prostaglandin E2 (PGE2) or DGLA itself and should be further evaluated.…”

Section: Omega-6 Fatty Acids In Aortic Valve Stenosismentioning

confidence: 96%

Fatty acids and aortic valve stenosis

Plunde

Bäck

2021

Kardiol Pol

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Celastrol Alleviates Aortic Valve Calcification Via Inhibition of NADPH Oxidase 2 in Valvular Interstitial Cells

Cited by 41 publications

References 54 publications

Attenuating Effects of Pyrogallol-Phloroglucinol-6,6-Bieckol on Vascular Smooth Muscle Cell Phenotype Changes to Osteoblastic Cells and Vascular Calcification Induced by High Fat Diet

Attenuating Effects of Pyrogallol-Phloroglucinol-6,6-Bieckol on Vascular Smooth Muscle Cell Phenotype Changes to Osteoblastic Cells and Vascular Calcification Induced by High Fat Diet

Glycogen synthase kinase-3β: a promising candidate in the fight against fibrosis

Fatty acids and aortic valve stenosis

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