Evidence map›Paper›PMID 25460366›Full record

ArticleVascular pharmacology2015

Alpha-lipoic acid activates eNOS through activation of PI3-kinase/Akt signaling pathway.

Zhekang Ying, Xiaoyun Xie, Minjie Chen, Kevin Yi, Sanjay Rajagopalan

Open access · greenAbstract read
In one paragraph

Article in Vascular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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  9. Iron Overload Damages the Endothelial MitochondriaOxidative medicine and cellular longevity · 2019
    Article
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  13. Article
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Zhekang YingDepartment of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China; Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: yingzhekang@hotmail.com.
Xiaoyun XieDivision of Geriatric Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China.
Minjie ChenDepartment of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China; Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Kevin YiDepartment of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Sanjay RajagopalanDepartment of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
University of Maryland, Baltimore · USShanghai East Hospital · CNTongji University · CN

Funding

Air Pollution and Hypertension: Vascular MechanismsR01ES015146 · NIEHS · UNIVERSITY OF MARYLAND BALTIMORE · PI RAJAGOPALAN, SANJAY · 2007 to 2018
$4.5M
Hypothalamic Inflammation and PM2.5 Exposure-Induced Insulin ResistanceR01ES024516 · NIEHS · UNIVERSITY OF MARYLAND BALTIMORE · PI YING, ZHEKANG · 2014 to 2018
$1.5M
Air Pollution Exposure/Atherosclerosis:Vascular MechanismR01ES013406 · NIEHS · OHIO STATE UNIVERSITY · PI RAJAGOPALAN, SANJAY · 2004 to 2007
$1.3M
NIEHS NIH HHS R01 ES013406NIEHS NIH HHS R01ES013406NIEHS NIH HHS R01 ES015146NIEHS NIH HHS R01ES015146NIEHS NIH HHS R01 ES024516NIEHS NIH HHS R01ES024516
6 · The paper itself

Abstract

backgroundLipoic acid (LA) exerts therapeutic effects on cardiovascular diseases. However, the mechanisms underlying these therapeutic effects remain elusive. Endothelial nitric oxide synthase (eNOS) plays a critical role in cardiovascular homeostasis. LA was shown to potently activate PI3-kinase/Akt pathway, and the latter is critical in the regulation of eNOS activity. In the present study, we test the hypothesis that LA improves endothelial function through PI3-kinase/Akt-mediated eNOS activation. METHODS AND

resultsWestern blot analysis showed that LA time- and dose-dependently induced phosphorylation of Akt and eNOS in human umbilical vein endothelial cells (HUVECs). Both PI3-kinase and Akt inhibitors abolished LA-induced eNOS phosphorylation, indicating that LA induces eNOS phosphorylation through the PI3-kinase/Akt pathway. This increase in eNOS phosphorylation was paralleled by an increase in NO release by HUVECs, supporting its relevance in eNOS activity regulation. Myograph analysis revealed that LA relaxed phenylephrine-induced contraction. Endothelium removal and NOS inhibition by L-NAME abolished this vasodilator action of LA, and Akt but not AMPK inhibition significantly reduced the vasodilator action of LA, indicating that it is mediated by PI3-kinase/Akt pathway-dependent activation of eNOS. Consistent with in vitro results, intraperitoneal injection with LA significantly increased plasma nitrite and nitrate levels in C57Bl/6j mice.

conclusionsLA activates eNOS through a PI3-kinase/Akt signaling pathway-dependent mechanism, offering a potential molecular basis for the therapeutic effects of LA on cardiovascular diseases.

Indexed as

AnimalsCells, CulturedEnzyme ActivationHumansHuman Umbilical Vein Endothelial CellsMaleMiceMice, Inbred C57BLNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionThioctic AcidNitric Oxide Synthase Type IIINOS3 protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktThioctic AcidAktEndotheliumeNOSLipoic acidPhosphorylation

Identifiers

PMID25460366
PMCPMC4331247
OpenAlexW2030152252

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.