ArticleArteriosclerosis, thrombosis, and vascular biology2017
mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice.
Open access · bronzeAbstract read
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 23 papers.
0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-weighted citation impact, top 14% of its field
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.
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.
Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Pathogenic Role of mTOR Signaling in Cardiometabolic Disease: Implications for Heart, Liver, and Kidney Dysfunction.Physiological research · 2025Review
- Double-Edged Signaling: FAK's Role in Aortic Dissection Progression.JACC. Basic to translational science · 2025Article
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Rapamycin reduces mineral density and promotes beneficial vascular remodeling in a murine model of severe medial arterial calcification.American journal of physiology. Heart and circulatory physiology · 2025Article
- Rapamycin Reduces Mineral Density and Promotes Beneficial Vascular Remodeling in a Murine Model of Severe Medial Arterial Calcification.bioRxiv : the preprint server for biology · 2025Article
- De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams-Beuren Syndrome.Journal of the American Heart Association · 2024Article
- Metformin Reduces the Progression of Atherogenesis by Regulating the Sestrin2-mTOR Pathway in Obese and Diabetic Rats.Journal of lipid and atherosclerosis · 2023Article
- mTOR inhibition prevents angiotensin II-induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice.JCI insight · 2022Article
- Roles of mTOR in thoracic aortopathy understood by complex intracellular signaling interactions.PLoS computational biology · 2021Article
- Regulatory role of mammalian target of rapamycin signaling in exosome secretion and osteogenic changes in smooth muscle cells lacking acid ceramidase gene.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Williams syndrome.Nature reviews. Disease primers · 2021Review
- The effect of anti‑HLA class I antibodies on the immunological properties of human glomerular endothelial cells and their modification by mTOR inhibition or GCN2 kinase activation.Molecular medicine reports · 2021Article
- Hypertension in Children and Adolescents with Turner Syndrome (TS), Neurofibromatosis 1 (NF1), and Williams Syndrome (WS).Current hypertension reports · 2021Review
- Effect of Microgroove Structure in PDMS-Based Silicone Implants on Biocompatibility.Frontiers in bioengineering and biotechnology · 2021Article
- Whole exome sequencing in patients with Williams-Beuren syndrome followed by disease modeling in mice points to four novel pathways that may modify stenosis risk.Human molecular genetics · 2020Article
- Everolimus Rescues the Phenotype of Elastin Insufficiency in Patient Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Caught between a "Rho" and a hard place: are CCN1/CYR61 and CCN2/CTGF the arbiters of microvascular stiffness?Journal of cell communication and signaling · 2020Review
- Aortic Strain Correlates with Elastin Fragmentation in Fibrillin-1 Hypomorphic Mice.Circulation reports · 2019Article
- Modeling elastin-associated vasculopathy with patient induced pluripotent stem cells and tissue engineering.Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Yang JiaoFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Guangxin LiFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Qingle LiFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Rahmat AliFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Lingfeng QinFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Wei LiFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Yibing QyangFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Daniel M GreifFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Arnar GeirssonFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
Jay D HumphreyFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.).
George TellidesFrom the Department of Surgery (Y.J., G.L., Q.L., R.A., L.Q., W.L., A.G., G.T.), Department of Internal Medicine (Y.Q., D.M.G.), and Vascular Biology and Therapeutics Program (Y.Q., D.M.G., A.G., J.D.H., G.T.), Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, Peking University People's Hospital, Beijing, P. R. China (Y.J., Q.L., W.L.); Department of Biomedical Engineering, Yale University, New Haven, CT (J.D.H.); and Veterans Affairs Connecticut Healthcare System, West Haven (G.T.). george.tellides@yale.edu.
Yale University · USPeking University · CNPeking University People's Hospital · CN
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MBiomechanical Simulation of Evolving Aortic Aneurysms for Designing InterventionR01HL086418 · NHLBI · YALE UNIVERSITY · PI HUMPHREY, JAY D. · 2008 to 2017
$3.8MMechanisms Underlying The Progression of Large Artery Stiffness in HypertensionR01HL105297 · NHLBI · YALE UNIVERSITY · PI FIGUEROA, CARLOS ALBERTO, HUMPHREY, JAY D. · 2010 to 2019
$3.0MHuman tissue-engineered blood vessels using induced pluripotent stem cellsR01HL116705 · NHLBI · YALE UNIVERSITY · PI QYANG, YIBING · 2013 to 2017
$2.0MPathological arterial muscularization and the role of integrinsR01HL125815 · NHLBI · YALE UNIVERSITY · PI GREIF, DANIEL · 2015 to 2018
$1.7MCharacterization of TGFB-Dependent Mechanoresponses by Aortic Smooth Muscle CellsR01HL134712 · NHLBI · YALE UNIVERSITY · PI HUMPHREY, JAY D., TELLIDES, GEORGE · 2017 to 2017
$599kNCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL086418NHLBI NIH HHS R01 HL105297NHLBI NIH HHS R01 HL116705NHLBI NIH HHS R01 HL125815NHLBI NIH HHS R01 HL134712
Abstract
objectiveElastin deficiency because of heterozygous loss of an APPROACH AND
resultsThoracic aortas of neonatal and juvenile mice with graded elastin deficiency exhibited increased signaling through both mTOR complex 1 and 2. Despite lower predicted wall stress, there was increased phosphorylation of focal adhesion kinase, suggestive of greater integrin activation, and increased transforming growth factor-β-signaling mediators, associated with increased collagen expression. Pharmacological blockade of mTOR by rapalogs did not improve luminal stenosis but reduced mechanosignaling (in delayed fashion after mTOR complex 1 inhibition), medial collagen accumulation, and stiffening of the aorta. Rapalog administration also retarded somatic growth, however, and precipitated neonatal deaths. Complementary, less-toxic strategies to inhibit mTOR via altered growth factor and nutrient responses were not effective.
conclusionsIn addition to previously demonstrated therapeutic benefits of rapalogs decreasing smooth muscle cell proliferation in the absence of elastin, we find that rapalogs also prevent aortic fibrosis and stiffening attributable to partial elastin deficiency. Our findings suggest that mTOR-sensitive perturbation of smooth muscle cell mechanosensing contributes to elastin aortopathy.
Indexed as
AnimalsAorta, ThoracicAortic DiseasesCell ProliferationCollagenElastinEverolimusFocal Adhesion Kinase 1Genetic Predisposition to DiseaseHumansImatinib MesylateMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Mechanotransduction, CellularMice, Inbred C57BLMice, KnockoutCollagenElastinEverolimusFocal Adhesion Kinase 1Imatinib MesylateMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2mTOR protein, mouseMultiprotein ComplexesProtein Kinase InhibitorsPtk2 protein, mouseSirolimusTOR Serine-Threonine Kinasesaortacollagenelastineverolimusmice
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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.