Protective role of α-lipoic acid in hyperuricemia-induced endothelial dysfunction

Zou, Hui; Wang, Huan; Liu, Tongmei; Li, Xiaojie; Zhu, Xiao-Duo; Wang, Zheng

doi:10.3892/etm.2017.4345

Cited by 23 publications

(19 citation statements)

References 35 publications

(37 reference statements)

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“…Another study reported that UA treatment of rats with middle cerebral artery occlusion enhanced vascular endothelial cell apoptosis ( 4 ). In our study, MAECs treated with different concentrations of UA showed increased expression of BAX and cleaved Caspase-3 and increases in the number of apoptotic cells, which confirmed the role of UA in promoting MAEC apoptosis as reported by a previous study ( 31 ). Furthermore, accumulating evidence has confirmed that miR-214 is a multifunctional miRNA in CVDs ( 32 – 35 ).…”

Section: Discussionsupporting

confidence: 92%

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miR-214 Protects Against Uric Acid-Induced Endothelial Cell Apoptosis

Yang

Zhu

et al. 2020

Front. Med.

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Background: Uric acid (UA) has been reported to be an important risk factor for cardiovascular diseases and can cause endothelial cell apoptosis through unclear mechanisms. Accumulating evidence has demonstrated that miR-214 plays a pivotal role in the pathogenesis of cardiovascular diseases. This study was to investigate the role of miR-214 in UA-induced endothelial cell apoptosis and the underlying mechanism. Material and methods: We enrolled 30 patients with hyperuricemia and 32 healthy controls and analyzed the levels of miR-214 in the serum of the participants. Then mouse aorta endothelial cells (MAECs) were treated with UA to induce cell apoptosis. An miR-214 mimic and a specific COX-2 inhibitor (NS398) were used to confirm the roles of these molecules in mediating UA-induced MAEC apoptosis or COX-2/PGE 2 cascade activation. Results: A significant reduction in circulating miR-214 in the hyperuricemia patients compared with the healthy controls, along with a negative correlation with UA levels was observed. In the MAECs, UA treatment strikingly increased apoptosis as shown by the upregulation of BAX and cleaved Caspase-3 and the increased number of apoptotic cells. Interestingly, the expression of COX-2 was also upregulated at both the protein and mRNA levels during UA-induced cell apoptosis. In addition, an miR-214 mimic blocked UA-induced MAEC apoptosis, COX-2 induction and PGE 2 secretion. The inhibition of COX-2 markedly ameliorated UA-induced apoptotic response and PGE 2 production in MAECs. Luciferase activity assays further confirmed that COX-2 is a target gene of miR-214 in endothelial cells. Conclusion: We concluded that miR-214 could alleviate UA-induced MAEC apoptosis possibly by inhibiting the COX-2/PGE 2 cascade.

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Section: Discussionsupporting

confidence: 92%

“…For this cell line, 300 µM UA in medium already mimicked hyperuricemia and caused obvious cytotoxicity. In agreement with this concept, 0.3 mM (300 µM) UA triggered apoptotic response in human umbilical vein endothelial cells (HUVECs) (31).…”

Section: Discussionsupporting

confidence: 69%

miR-214 Protects Against Uric Acid-Induced Endothelial Cell Apoptosis

Yang

Zhu

et al. 2020

Front. Med.

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“…Our results are also in accordance with several animal studies. Accordingly, in a study ALA supplementation significantly attenuated oxidative stress and inhibited apoptosis in rat model of hyperuricemia-induced aortic endothelial cells dysfunction (Zou et al, 2017). In another study, dietary ALA could beneficially improve oxidative stress and inflammation and restore nitric oxide (NO) bioavailability in mice exposed to Chronic Intermittent Hypoxia (Badran, Abuyassin, Golbidi, Ayas, & Laher, 2019).…”

Section: Discussionmentioning

confidence: 99%

The effect of Alpha‐lipoic acid supplementation on endothelial function: A systematic review and meta‐analysis

Jalilpiran

Hajishafiee

Khorshidi

et al. 2020

Phytotherapy Research

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There is evidence that alpha-lipoic acid (ALA) supplementation plays an important role in preventing cardiovascular diseases. However, its effect, specifically, on endothelial function (EF) is unclear. Therefore, this systematic review and meta-analysis aimed to evaluate the effects of ALA supplementation on EF. Databases including PubMed/Medline, Scopus, and ISI Web of Science were searched to identify eligible publications from inception up to April 2020. Randomized controlled trials assessing the effect of ALA supplementation on flow-mediated dilation (FMD) levels in adults were included. The pooled results were obtained using the random-effects model and are expressed as weighted mean differences (WMD) with 95% confidence intervals (CI). Five studies including six effect sizes and 300 participants were included.ALA supplementation significantly increased FMD levels by 2.36% (95% CI:1.21-3.51; p < .001), compared with the control. Subgroup analyses suggested that the effects of ALA on FMD could be changed by age and health status of the participants. Dose-response analysis also showed that ALA dosage had a significant nonlinear effect on FMD levels. The results showed that ALA supplementation appears to improve the EF. However, the role of ALA supplementation in improving other biomarkers of EF requires further research.

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“…Eredményeik alapján az ALA adásával csökkent a ROS szintje, fokozódott az endothelialis NO-szintáz aktivitás, nőtt az ATP és a mitokondriális DNS mennyisége a patkányaorta endothelialis sejtjeiben. 42 Több humán vizsgálat az ALA-kezelés kedvező hatására utalt az endothelműködés tekintetében 1-es és 2-es típusú cukorbetegekben, 43,44 azonban további experimentális és randomizált, placebo-kontrollált vizsgálatok szükségesek az ALA endotheliumra kifejtett hatásának tisztázására DNP-ben.…”

Section: A Pon1 Paraoxonáz Enzim éS Az Endothelialis Diszfunkció…unclassified

A PON1 paraoxonáz enzim és az endothelialis diszfunkciót jellemző markerek változása alfa-liponsav-kezelés hatására diabeteses neuropathiában

Sztanek¹,

Molnár²,

Bányai³

et al. 2018

Diabetologia Hungarica

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Az oxidatív stressz fontos szerepet játszik a 2-es típusú cukorbetegség microvascularis szövődményeinek kialakulásában. A diabeteses neuropathia az egyik leggyakrabban felismerhető szövődmény, és a fokozott oxidatív stressz elősegíti a progreszszióját. A HDL-hez kötött PON1 paraoxonáz enzim többek között az oxidatív folyamatok csökkentésével fejti ki antioxidáns hatását. Az aszimmetrikus dimetil-arginin (ADMA) endogén NO-szintáz-inhibitorként hasznosítható markernek tűnik az endothelialis diszfunkció jellemzésére. A legújabb irodalmi adatok alapján szoros összefüggés mutatható ki az emelkedett ADMA-szint és az oxidatív stressz mértéke között. Az oxidatív folyamatok megemelik a VCAM-1 és ICAM-1 sejtadhéziós molekulák szintjét. Az alfa-liponsav (ALA) hatékony antioxidáns terápiaként alkalmazható a diabeteses neuropathia kezelésében, elősegíti a sejtszintű antioxidáns védelmet és gyulladáscsökkentő hatása is lehet. Vizsgálatunk során 38 diabeteses neuropathiás betegnél (14 férfi és 24 nő) vizsgáltuk az oxidatív stressz markereként a PON1 paraoxonáz aktivitást, az AD-MA-t, a nitrogén-monoxid koncentrációját és a VCAM-1/ICAM-1 szinteket ALA-kezelés megkezdése előtt és napi 600-1200 mg kezelés folyamán a 6. hónapban. A PON1 paraoxonáz aktivitás szignifikánsan magasabb (p<0,05), az ADMA-és az NOszintek szignifikánsan alacsonyabbak (p<0,001 és p<0,01) voltak diabeteses neuropathiás betegekben hat hónapos ALAterápia után. A PON1 paraoxonáz aktivitás a responder csoportban volt jelentősen magasabb a non-responderekhez képest (p<0,001). Az áramérzet-küszöbérték javulásával szorosan korrelált a magasabb PON1 paraoxonáz aktivitás (p<0,05) és az alacsonyabb ADMA-szint (p<0,05) a responderekben, de nem volt összefüggés a non-responder csoportban. Lineáris korrelációt figyeltünk meg a szérum nitrogén-monoxid-és ADMA-koncentrációja között a responder csoportban (p<0,05). A csökkent PON1 paraoxonáz aktivitás, az endothelialis diszfunckció és a fokozott oxidatív stressz növeli a diabeteses neuropathia progresszióját, és az alfa-liponsav-kezelés figyelemreméltó hatást fejthet ki az oxidatív státuszra. ■ Kulcsszavak: paraoxonáz, endothelialis diszfunkció, alfa-liponsav, diabeteses neuropathia Changes of PON1 paraoxonase enzyme activity and markers of endothelial dysfunction after treatment of diabetic neuropathy with alpha-lipoic acidSummary: Oxidative stress plays a pivotal role in the development of microvascular consequences of type 2 diabetes. Diabetic neuropathy has emerged as one of the most common complications of diabetes mellitus and increased oxidative stress has been related to the progression of diabetic neuropathy. Paraoxonase (PON1), an antioxidant enzyme, may have an important role in decreasing oxidative stress. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, represents a novel risk factor for the development of endothelial dysfunction and several studies have indicated substantial interaction between oxidative stress and increased ADMA levels. Oxidative stress leads to endothelial c...

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Protective role of α-lipoic acid in hyperuricemia-induced endothelial dysfunction

Cited by 23 publications

References 35 publications

miR-214 Protects Against Uric Acid-Induced Endothelial Cell Apoptosis

miR-214 Protects Against Uric Acid-Induced Endothelial Cell Apoptosis

The effect of Alpha‐lipoic acid supplementation on endothelial function: A systematic review and meta‐analysis

A PON1 paraoxonáz enzim és az endothelialis diszfunkciót jellemző markerek változása alfa-liponsav-kezelés hatására diabeteses neuropathiában

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