Evidence map›Paper›PMID 27256105›Full record

ArticleCirculation research2016

Ablation of Adenosine Monophosphate-Activated Protein Kinase α1 in Vascular Smooth Muscle Cells Promotes Diet-Induced Atherosclerotic Calcification In Vivo.

Zhejun Cai, Ye Ding, Miao Zhang, Qiulun Lu, Shengnan Wu, Huaiping Zhu, Ping Song, Ming-Hui Zou

RetractedErratum issuedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

57 citing papers in PubMed, 97 citations in OpenAlex.

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  13. Signalling mechanisms and cellular functions of SUMO.Nature reviews. Molecular cell biology · 2022
    Review
  14. New insight into dyslipidemia-induced cellular senescence in atherosclerosis.Biological reviews of the Cambridge Philosophical Society · 2022
    Review
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  16. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 2 countries.

Zhejun CaiFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Z.C., Y.D., Q.L., S.W., H.Z., P.S., M.-H.Z.); Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China (Z.C.); and Department of Medicine, University of Oklahoma Health Sciences Center (M.Z.).
Ye DingFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Z.C., Y.D., Q.L., S.W., H.Z., P.S., M.-H.Z.); Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China (Z.C.); and Department of Medicine, University of Oklahoma Health Sciences Center (M.Z.).
Miao ZhangFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Z.C., Y.D., Q.L., S.W., H.Z., P.S., M.-H.Z.); Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China (Z.C.); and Department of Medicine, University of Oklahoma Health Sciences Center (M.Z.).
Qiulun LuFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Z.C., Y.D., Q.L., S.W., H.Z., P.S., M.-H.Z.); Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China (Z.C.); and Department of Medicine, University of Oklahoma Health Sciences Center (M.Z.).
Shengnan WuFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Z.C., Y.D., Q.L., S.W., H.Z., P.S., M.-H.Z.); Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China (Z.C.); and Department of Medicine, University of Oklahoma Health Sciences Center (M.Z.).
Huaiping ZhuFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Z.C., Y.D., Q.L., S.W., H.Z., P.S., M.-H.Z.); Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China (Z.C.); and Department of Medicine, University of Oklahoma Health Sciences Center (M.Z.).
Ping SongFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Z.C., Y.D., Q.L., S.W., H.Z., P.S., M.-H.Z.); Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China (Z.C.); and Department of Medicine, University of Oklahoma Health Sciences Center (M.Z.).
Ming-Hui ZouFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Z.C., Y.D., Q.L., S.W., H.Z., P.S., M.-H.Z.); Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China (Z.C.); and Department of Medicine, University of Oklahoma Health Sciences Center (M.Z.). mzou@gsu.edu.
Zhejiang Medical and Health Group Hangzhou Hospital · CN

Funding

Autophagy and VSMC migrationR01HL132500 · NHLBI · GEORGIA STATE UNIVERSITY · PI XIE, ZHONGLIN, ZOU, MING-HUI · 2016 to 2019
$2.7M
Prevention of High Fat Diet-Induced Vascular InjuryR01HL105157 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZOU, MING-HUI · 2010 to 2014
$1.8M
NHLBI NIH HHS R01 HL105157NHLBI NIH HHS R01 HL132500
6 · The paper itself

Abstract

rationaleAtherosclerotic calcification is highly linked with plaque rapture. How calcification is regulated is poorly characterized.

objectiveWe sought to determine the contributions of AMP-activated protein kinase (AMPK) in atherosclerotic calcification. METHODS AND

resultsAortic calcification was evaluated in aortic roots and brachiocephalic arteries of atherosclerotic prone ApoE(-/-) mice or in mice with dual deficiencies of ApoE and AMPKα isoforms in whole body (ApoE(-/-)/AMPKα1(-/-) and ApoE(-/-)/AMPKα2(-/-)) or vascular smooth muscle cell (VSMC)-specific or macrophage-specific knockout of AMPKα1 fed with Western diet for 24 weeks. Genetic deficiency of AMPKα1 but not of AMPKα2 promoted atherosclerotic calcification and the expression of Runx2 (Runt-related transcription factor). Conversely, chronic administration of metformin, which activated AMPK, markedly reduced atherosclerotic calcification and Runx2 expression in ApoE(-/-) mice but had less effects in ApoE(-/-)/AMPKα1(-/-) mice. Furthermore, VSMC-specific but not macrophage-specific ablation of AMPKα1 promoted aortic calcification in vivo. Ablation of AMPKα1 in VSMC prevented Runx2 from proteasome degradation in parallel with aberrant osteoblastic differentiation of VSMC, whereas AMPK activation promoted Runx2 post-translational modification by small ubiquitin-like modifier (SUMO, SUMOylation), which is associated with its instability. Mechanically, we found that AMPKα1 directly phosphorylated protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, at serine 510, to promote its SUMO E3-ligase activity. Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed metformin-induced Runx2 SUMOylation and subsequently prevented metformin's effect on reducing oxidized low-density lipoprotein-triggered Runx2 expression in VSMC.

conclusionsAMPKα1 phosphorylated protein inhibitor of activated STAT-1 to promote Runx2 SUMOylation and subsequently lead to its instability. AMPKα1 deficiency in VSMC increased Runx2 expression and promoted atherosclerotic calcification in vivo.

Indexed as

AMP-Activated Protein KinasesAnimalsAtherosclerosisCells, CulturedDiet, WesternMaleMiceMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleVascular CalcificationAMP-Activated Protein KinasesPrkaa1 protein, mouseAMP-activated protein kinasesatherosclerosismuscle, smooth, vascularosteoblastsosteogenesisprotein inhibitors of activated STATRunx2 proteinsumoylation

Identifiers

PMID27256105
OpenAlexW2417405563

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.