Evidence map›Paper›PMID 27439892›Full record

ArticleCirculation research2016

AMP-Activated Protein Kinase Alpha 2 Deletion Induces VSMC Phenotypic Switching and Reduces Features of Atherosclerotic Plaque Stability.

Ye Ding, Miao Zhang, Wencheng Zhang, Qiulun Lu, Zhejun Cai, Ping Song, Imoh Sunday Okon, Lei Xiao, Ming-Hui Zou

Open access · greenAbstract read
PubMed Full text at PMC 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. Cited by 48 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Extreme Diversity of the Human Vascular Mesenchymal Cell Landscape.Journal of the American Heart Association · 2020
    Pooled it
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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

9 authors at 1 institution in 1 country.

Ye DingFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.).
Miao ZhangFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.).
Wencheng ZhangFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.).
Qiulun LuFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.).
Zhejun CaiFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.).
Ping SongFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.).
Imoh Sunday OkonFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.).
Lei XiaoFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.).
Ming-Hui ZouFrom the Center for Molecular and Translational Medicine, Georgia State University, Atlanta (Y.D., Q.L., Z.C., P.S., I.S.O., L.X., M.-H.Z.); Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (M.Z.); and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China (W.Z.). mzou@gsu.edu.
University of Oklahoma Health Sciences Center · US

Funding

Reactive Nitrogen species and Diabetic Endothelial DysfunctionR01HL079584 · NHLBI · UNIVERSITY OF TENNESSEE KNOXVILLE · PI ZOU, MING-HUI · 2004 to 2021
$7.3M
Inflammasome and unstable atherosclerotic plaquesR01HL089920 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZOU, MING-HUI · 2008 to 2022
$6.9M
AMP-Activated Protein Kinase in DiabetesR01HL080499 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZOU, MING-HUI · 2006 to 2019
$5.8M
Controlling VSMC Proliferation and MigrationR01HL110488 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZOU, MING-HUI · 2011 to 2020
$3.9M
Oxidant stress and diabetic endothelial dysfunctionR01HL074399 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZOU, MING-HUI · 2005 to 2013
$3.2M
SNRK in ischemic vascular diseasesR01HL142287 · NHLBI · GEORGIA STATE UNIVERSITY · PI XIE, ZHONGLIN, ZOU, MING-HUI · 2018 to 2022
$3.0M
FUNDC1 and diabetic cardiomyopathyR01HL137371 · NHLBI · GEORGIA STATE UNIVERSITY · PI XIE, ZHONGLIN, ZOU, MING-HUI · 2017 to 2020
$2.8M
MKP1, VSMC, and Vascular RemodelingR01HL140954 · NHLBI · GEORGIA STATE UNIVERSITY · PI SONG, PING, ZOU, MING-HUI · 2018 to 2021
$2.8M
Autophagy and VSMC migrationR01HL132500 · NHLBI · GEORGIA STATE UNIVERSITY · PI XIE, ZHONGLIN, ZOU, MING-HUI · 2016 to 2019
$2.7M
Suppression of Autophagy-Dependent Clearance Mitochondria in Type 2 DiabetesR01HL128014 · NHLBI · GEORGIA STATE UNIVERSITY · PI XIE, ZHONGLIN, ZOU, MING-HUI · 2015 to 2018
$2.4M
Liver kinase B1 in angiogenesisR01CA213022 · NCI · GEORGIA STATE UNIVERSITY · PI ZOU, MING-HUI · 2017 to 2021
$2.3M
Prevention of High Fat Diet-Induced Vascular InjuryR01HL105157 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZOU, MING-HUI · 2010 to 2014
$1.8M
NCI NIH HHS R01 CA213022NHLBI NIH HHS R01 HL074399NHLBI NIH HHS R01 HL079584NHLBI NIH HHS R01 HL080499NHLBI NIH HHS R01 HL089920NHLBI NIH HHS R01 HL096032NHLBI NIH HHS R01 HL105157NHLBI NIH HHS R01 HL110488NHLBI NIH HHS R01 HL128014NHLBI NIH HHS R01 HL132500NHLBI NIH HHS R01 HL137371NHLBI NIH HHS R01 HL140954NHLBI NIH HHS R01 HL142287NIA NIH HHS R01 AG047776
6 · The paper itself

Abstract

rationaleAMP-activated protein kinase (AMPK) has been reported to play a protective role in atherosclerosis. However, whether AMPKα2 controls atherosclerotic plaque stability remains unknown.

objectiveThe aim of this study was to evaluate the impact of AMPKα2 deletion on atherosclerotic plaque stability in advanced atherosclerosis at the brachiocephalic arteries and to elucidate the underlying mechanisms. METHODS AND

resultsFeatures of atherosclerotic plaque stability and the markers for contractile or synthetic vascular smooth muscle cell (VSMC) phenotypes were monitored in the brachiocephalic arteries from Apoe(-/-)AMPKα2(-/-) mice or VSMC-specific AMPKα2(-/-) mice in an Apoe(-/-) background (Apoe(-/-)AMPKα2(sm-/-)) fed Western diet for 10 weeks. We identified that Apoe(-/-)AMPKα2(-/-) mice and Apoe(-/-)AMPKα2(sm-/-) mice exhibited similar unstable plaque features, aggravated VSMC phenotypic switching, and significant upregulation of Kruppel-like factor 4 (KLF4) in the plaques located in the brachiocephalic arteries compared with those found in Apoe(-/-) and Apoe(-/-)AMPKα2(sm+/+) control mice. Pravastatin, an AMPK activator, suppressed VSMC phenotypic switching and alleviated features of atherosclerotic plaque instability in Apoe(-/-)AMPKα2(sm+/+) mice, but not in Apoe(-/-)AMPKα2(sm-/-) mice. VSMC isolated from AMPKα2(-/-) mice displayed a significant reduction of contractile proteins(smooth muscle actin-α, calponin, and SM-MHC [smooth muscle-mysion heavy chain]) in parallel with increased detection of synthetic proteins (vimentin and osteopontin) and KLF4, as observed in vivo. KLF4-specific siRNA abolished AMPKα2 deletion-induced VSMC phenotypic switching. Furthermore, pharmacological or genetic inhibition of nuclear factor-κB significantly decreased KLF4 upregulation in VSMC from AMPKα2(-/-) mice. Finally, we found that AMPKα2 deletion markedly promoted the binding of nuclear factor-κBp65 to KLF4 promoter.

conclusionsThis study demonstrated that AMPKα2 deletion induces VSMC phenotypic switching and promotes features of atherosclerotic plaque instability in nuclear factor-κB-KLF4-dependent manner.

Indexed as

Gene DeletionPhenotypeAMP-Activated Protein KinasesAnimalsDiet, WesternKruppel-Like Factor 4MaleMiceMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MusclePlaque, AtheroscleroticAMP-Activated Protein KinasesKlf4 protein, mouseKruppel-Like Factor 4Prkaa2 protein, mouseAMP-activated protein kinasesatherosclerosis

Identifiers

PMID27439892
PMCPMC6265658
OpenAlexW2488479442

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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.