ArticleArteriosclerosis, thrombosis, and vascular biology2017
Opposing Actions of AKT (Protein Kinase B) Isoforms in Vascular Smooth Muscle Injury and Therapeutic Response.
Open access · bronzeAbstract readComparative Study
In one paragraph
Article in Arteriosclerosis, thrombosis, and vascular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
What it found
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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.
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.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Investigation of Akt1 behavior on gold surface from molecular dynamics insight.Scientific reports · 2025Article
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- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- Vascular smooth muscle cells in intimal hyperplasia, an update.Frontiers in physiology · 2022Review
- hiPSC Modeling of Lineage-Specific Smooth Muscle Cell Defects Caused byCirculation · 2021Article
- TMEM16A channel upregulation in arterial smooth muscle cells produces vasoconstriction during diabetes.American journal of physiology. Heart and circulatory physiology · 2021Article
- Targeting smooth muscle cell phenotypic switching in vascular disease.JVS-vascular science · 2021Review
- Everolimus Rescues the Phenotype of Elastin Insufficiency in Patient Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Current perspective on the regulation of FOXO4 and its role in disease progression.Cellular and molecular life sciences : CMLS · 2020Review
- Smooth muscle cell-specific fibronectin-EDA mediates phenotypic switching and neointimal hyperplasia.The Journal of clinical investigation · 2020Article
- Metabolism, Obesity, and Diabetes Mellitus.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- The unconventional role of Akt1 in the advanced cancers and in diabetes-promoted carcinogenesis.Pharmacological research · 2019Review
- Hippo and Hyperplasia.Circulation research · 2019Article
- PI3Kγ (Phosphoinositide 3-Kinase γ) Regulates Vascular Smooth Muscle Cell Phenotypic Modulation and Neointimal Formation Through CREB (Cyclic AMP-Response Element Binding Protein)/YAP (Yes-Associated Protein) Signaling.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- LMO7 Is a Negative Feedback Regulator of Transforming Growth Factor β Signaling and Fibrosis.Circulation · 2019Article
- Reporting Sex and Sex Differences in Preclinical Studies.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Yu JinFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Yi XieFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Allison C OstrikerFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Xinbo ZhangFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Renjing LiuFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Monica Y LeeFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Kristen L LeslieFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Waiho TangFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Jing DuFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Seung Hee LeeFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Yingdi WangFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
William C SessaFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
John HwaFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Jun YuFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.).
Kathleen A MartinFrom the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine (Y.J., Y.X., A.C.O., K.L.L., W.T., J.D., S.H.L., Y.W., J.H., K.A.M.) and Department of Pharmacology (Y.J., Y.X., A.C.O., M.Y.L., K.L.L., W.C.S., K.A.M.), Yale University, New Haven, CT; Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT (X.Z.); Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, Australia (R.L.); Sydney Medical School, University of Sydney, Sydney, Australia (R.L.); and Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (J.Y.). kathleen.martin@yale.edu.
Centenary Institute · AUYale University · USUniversity of Sydney · AU
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MPilot Study: POPULATION PHARMACOLOGYU54HL117798 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BLAIR, IAN ALEXANDER · 2012 to 2016
$18.5MNovel targets of rapamycin and Akt in vascular smooth muscle cell differentiationR01HL091013 · NHLBI · YALE UNIVERSITY · PI MARTIN, KATHLEEN ANN · 2008 to 2017
$4.1MHyperglycemia, thromboxane and platelet activity in diabetes mellitusR01HL115247 · NHLBI · YALE UNIVERSITY · PI HWA, JOHN · 2012 to 2019
$3.8MPlatelet Mitochondrial Function in Health and DiseaseR01HL122815 · NHLBI · YALE UNIVERSITY · PI HWA, JOHN · 2015 to 2023
$3.7MPharmacogenetics of the human prostacyclin receptor.R01HL074190 · NHLBI · YALE UNIVERSITY · PI HWA, JOHN · 2004 to 2013
$3.3MEpigenetic control of vascular smooth muscle in cardiovascular diseaseR01HL119529 · NHLBI · YALE UNIVERSITY · PI MARTIN, KATHLEEN ANN · 2014 to 2017
$1.7MRegulation of vascular smooth muscle cell plasticityR01HL118430 · NHLBI · YALE UNIVERSITY · PI MARTIN, KATHLEEN ANN · 2014 to 2017
$1.7MER-associated protein Reticulon in atherosclerosisR01HL126933 · NHLBI · YALE UNIVERSITY · PI YU, JUN · 2015 to 2018
$1.6MRole of RTN-4 in AtherosclerosisR56HL117064 · NHLBI · YALE UNIVERSITY · PI YU, JUN · 2013 to 2013
$416kAmerican Heart Association-American Stroke Association 0930157NNCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL074190NHLBI NIH HHS R01 HL091013NHLBI NIH HHS R01 HL115247NHLBI NIH HHS R01 HL118430NHLBI NIH HHS R01 HL119529NHLBI NIH HHS R01 HL122815NHLBI NIH HHS R01 HL126933NHLBI NIH HHS R56 HL117064NHLBI NIH HHS U54 HL117798
Abstract
objectiveDrug-eluting stent delivery of mTORC1 (mechanistic target of rapamycin complex 1) inhibitors is highly effective in preventing intimal hyperplasia after coronary revascularization, but adverse effects limit their use for systemic vascular disease. Understanding the mechanism of action may lead to new treatment strategies. We have shown that rapamycin promotes vascular smooth muscle cell differentiation in an AKT2-dependent manner in vitro. Here, we investigate the roles of AKT (protein kinase B) isoforms in intimal hyperplasia. APPROACH AND
resultsWe found that germ-line-specific or smooth muscle-specific deletion of
conclusionsOur data reveal opposing roles for AKT isoforms in smooth muscle cell remodeling. AKT2 is required for rapamycin's therapeutic inhibition of intimal hyperplasia, likely mediated in part through AKT2-specific regulation of MYOCD via FOXO4. Because AKT2 signaling is impaired in diabetes mellitus, this work has important implications for rapamycin therapy, particularly in diabetic patients.
Indexed as
NeointimaAnimalsBinding SitesCell Cycle ProteinsCell DifferentiationCell MovementCell ProliferationCells, CulturedDisease Models, AnimalForkhead Transcription FactorsGene Expression RegulationGenetic Predisposition to DiseaseHumansMice, KnockoutMuscle, Smooth, VascularMyocardinAKT1 protein, humanAkt1 protein, mouseAKT2 protein, humanAkt2 protein, mouseCell Cycle ProteinsForkhead Transcription FactorsFOXO4 protein, humanMyocardinNuclear ProteinsProto-Oncogene Proteins c-aktRNA, MessengerSirolimusTrans-ActivatorsTranscription Factorsdrug-eluting stentsgene expressionhyperplasiamuscle, smooththerapeutics
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