Evidence map›Paper›PMID 27758765›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

AMP-Activated Protein Kinase and Sirtuin 1 Coregulation of Cortactin Contributes to Endothelial Function.

Tzu-Pin Shentu, Ming He, Xiaoli Sun, Jianlin Zhang, Fan Zhang, Brendan Gongol, Traci L Marin, Jiao Zhang, Liang Wen, Yinsheng Wang and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Review
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  5. Article
  6. Review
  7. Review
  8. FAIMS Enhances the Detection of PTM Crosstalk Sites.Journal of proteome research · 2022
    Article
  9. Review
  10. Observational
  11. [Angiotensin Ⅱ inhibits AMPK/SIRT1 pathway by inducing oxidative stress in RAW264.7 macrophages].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021
    Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Shear stress regulation of miR-93 and miR-484 maturation through nucleolin.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  18. Review
  19. Atheroprone flow enhances the endothelial-to-mesenchymal transition.American journal of physiology. Heart and circulatory physiology · 2018
    Article
  20. Reporting Sex and Sex Differences in Preclinical Studies.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 3 countries.

Tzu-Pin ShentuFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Ming HeFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Xiaoli SunFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Jianlin ZhangFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Fan ZhangFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Brendan GongolFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Traci L MarinFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Jiao ZhangFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Liang WenFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Yinsheng WangFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Gregory G GearyFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
Yi ZhuFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
David A JohnsonFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.).
John Y-J ShyyFrom the Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (T.-P.S., M.H., J.Z., J.Z.; L.W., J.Y.-J.S.); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (X.S., Y.Z.); Department of Chemistry, University of California, Riverside (F.Z., Y.W.); Department of Cardiopulmonary Sciences, Schools of Allied Health, Loma Linda University, CA (B.G., T.L.M.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.G.); and Division of Biomedical Sciences, University of California, Riverside (D.A.J.). jshyy@ucsd.edu.
University of California, Riverside · US

Funding

Systems Biology Analyses for Hemodynamic Regulation of Vascular HomeostasisR01HL108735 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2012 to 2024
$13.4M
Shear Regulation of MicroRNA Transportomes and Targetomes in Vascular HomeostasisR01HL106579 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2011 to 2022
$8.3M
Shear Stress, AMPK, and Endothelial FunctionsR01HL089940 · NHLBI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SHYY, JOHN YJ · 2009 to 2013
$1.9M
Flow-Induced Endothelial Innate Immunity and Atherosclerosis SusceptibilityR01HL125643 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHYY, JOHN YJ · 2016 to 2019
$1.7M
Repair of Radiation-Induced Crosslink Lesions of DNAR01ES019873 · NIEHS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI WANG, YINSHENG · 2012 to 2016
$1.5M
Shear stress, SIRT1, and Arterial StiffeningR01HL105318 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHYY, JOHN YJ · 2010 to 2013
$1.5M
NHLBI NIH HHS R01 HL089940NHLBI NIH HHS R01 HL105318NHLBI NIH HHS R01 HL106579NHLBI NIH HHS R01 HL108735NHLBI NIH HHS R01 HL125643NIEHS NIH HHS R01 ES019873
6 · The paper itself

Abstract

objectiveCortactin translocates to the cell periphery in vascular endothelial cells (ECs) on cortical-actin assembly in response to pulsatile shear stress. Because cortactin has putative sites for AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) deacetylation, we examined the hypothesis that AMPK and SIRT1 coregulate cortactin dynamics in response to shear stress. APPROACH AND

resultsAnalysis of the ability of AMPK to phosphorylate recombinant cortactin and oligopeptides whose sequences matched AMPK consensus sequences in cortactin pointed to Thr-401 as the site of AMPK phosphorylation. Mass spectrometry confirmed Thr-401 as the site of AMPK phosphorylation. Immunoblot analysis with AMPK siRNA and SIRT1 siRNA in human umbilical vein ECs and EC-specific AMPKα2 knockout mice showed that AMPK phosphorylation of cortactin primes SIRT1 deacetylation in response to shear stress. Immunoblot analyses with cortactin siRNA in human umbilical vein ECs, phospho-deficient T401A and phospho-mimetic T401D mutant, or aceto-deficient (9K/R) and aceto-mimetic (9K/Q) showed that cortactin regulates endothelial nitric oxide synthase activity. Confocal imaging and sucrose-density gradient analyses revealed that the phosphorylated/deacetylated cortactin translocates to the EC periphery facilitating endothelial nitric oxide synthase translocation from lipid to nonlipid raft domains. Knockdown of cortactin in vitro or genetic reduction of cortactin expression in vivo in mice substantially decreased the endothelial nitric oxide synthase-derived NO bioavailability. In vivo, atherosclerotic lesions increase in ApoE

conclusionsAMPK phosphorylation of cortactin followed by SIRT1 deacetylation modulates the interaction of cortactin and cortical-actin in response to shear stress. Functionally, this AMPK/SIRT1 coregulated cortactin-F-actin dynamics is required for endothelial nitric oxide synthase subcellular translocation/activation and is atheroprotective.

Indexed as

AcetylationActinsAMP-Activated Protein KinasesAnimalsApolipoproteins EAtherosclerosisCells, CulturedCortactinDisease Models, AnimalEndothelial CellsGenotypeHumansMaleMice, KnockoutNitric Oxide Synthase Type IIIPhenotypeActinsAMP-Activated Protein KinasesApolipoproteins ECortactinCTTN protein, humanCttn protein, mouseNitric Oxide Synthase Type IIINOS3 protein, humanNos3 protein, mousePRKAA2 protein, humanPrkaa2 protein, mouseSIRT1 protein, humanSirt1 protein, mouseSirtuin 1AMP-activated protein kinasesatherosclerosiscaveolin-1cortactinnitric oxide synthase type III

Identifiers

PMID27758765
PMCPMC5391843
OpenAlexW2528037656

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.