Evidence map›Paper›PMID 25916723›Full record

ArticleHypertension (Dallas, Tex. : 1979)2015

Role of epidermal growth factor receptor and endoplasmic reticulum stress in vascular remodeling induced by angiotensin II.

Takehiko Takayanagi, Tatsuo Kawai, Steven J Forrester, Takashi Obama, Toshiyuki Tsuji, Yamato Fukuda, Katherine J Elliott, Douglas G Tilley, Robin L Davisson, Joon-Young Park and 1 more

Open access · greenAbstract readComparative Study
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.8field-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

64 citing papers in PubMed, 97 citations in OpenAlex.

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  17. Mitochondrial fission inhibition protects against hypertension induced by angiotensin II.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
    Article
  18. Review
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4 more citing papers are in PubMed but not listed here.

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

11 authors at 1 institution in 1 country.

Takehiko TakayanagiFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Tatsuo KawaiFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Steven J ForresterFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Takashi ObamaFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Toshiyuki TsujiFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Yamato FukudaFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Katherine J ElliottFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Douglas G TilleyFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Robin L DavissonFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Joon-Young ParkFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.).
Satoru EguchiFrom the Department of Physiology, Cardiovascular Research Center (T. Takayanagi, T.K., S.J.F., T.O., T. Tsuji, Y.F., K.J.E., J.-Y.P., S.E.) and Department of Pharmacology, Center for Translational Medicine (D.G.T.), Temple University School of Medicine, Philadelphia, PA; Department of Kinesiology, Temple University College of Public Health, Philadelphia, PA (S.J.F., J.-Y.P.); and Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY (R.L.D.). seguchi@temple.edu.
Temple University · US

Funding

Role of the brain Renin-Angiotensin Sys. in Cardiovas and Metabolic RegulationP01HL084207 · NHLBI · UNIVERSITY OF IOWA · PI SIGMUND, CURT DANIEL · 2007 to 2022
$30.2M
Molecular Mechanisms of Cardiac beta1AR-EGFR Association and SignalingR01HL105414 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI TILLEY, DOUGLAS · 2011 to 2019
$3.4M
ErbB Activation via a Metalloprotease by Angiotensin IIR01HL076770 · NHLBI · VANDERBILT UNIVERSITY · PI EGUCHI, SATORU · 2004 to 2012
$2.8M
Functional implications of fluid shear stress-induced mitochondrial remodelingR01HL126952 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI PARK, JOON YOUNG · 2015 to 2019
$2.1M
Mechanism of Hypertensive Vascular Remodeling and End-Organ DamageR01HL133248 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI EGUCHI, SATORU · 2016 to 2019
$1.8M
NHLBI NIH HHS HL076770NHLBI NIH HHS HL105414NHLBI NIH HHS P01 HL084207NHLBI NIH HHS R01 HL076770NHLBI NIH HHS R01 HL105414NHLBI NIH HHS R01 HL126952NHLBI NIH HHS R01 HL133248
6 · The paper itself

Abstract

The mechanisms by which angiotensin II (AngII) elevates blood pressure and enhances end-organ damage seem to be distinct. However, the signal transduction cascade by which AngII specifically mediates vascular remodeling such as medial hypertrophy and perivascular fibrosis remains incomplete. We have previously shown that AngII-induced epidermal growth factor receptor (EGFR) transactivation is mediated by disintegrin and metalloproteinase domain 17 (ADAM17), and that this signaling is required for vascular smooth muscle cell hypertrophy but not for contractile signaling in response to AngII. Recent studies have implicated endoplasmic reticulum (ER) stress in hypertension. Interestingly, EGFR is capable of inducing ER stress. The aim of this study was to test the hypothesis that activation of EGFR and ER stress are critical components required for vascular remodeling but not hypertension induced by AngII. Mice were infused with AngII for 2 weeks with or without treatment of EGFR inhibitor, erlotinib, or ER chaperone, 4-phenylbutyrate. AngII infusion induced vascular medial hypertrophy in the heart, kidney and aorta, and perivascular fibrosis in heart and kidney, cardiac hypertrophy, and hypertension. Treatment with erlotinib as well as 4-phenylbutyrate attenuated vascular remodeling and cardiac hypertrophy but not hypertension. In addition, AngII infusion enhanced ADAM17 expression, EGFR activation, and ER/oxidative stress in the vasculature, which were diminished in both erlotinib-treated and 4-phenylbutyrate-treated mice. ADAM17 induction and EGFR activation by AngII in vascular cells were also prevented by inhibition of EGFR or ER stress. In conclusion, AngII induces vascular remodeling by EGFR activation and ER stress via a signaling mechanism involving ADAM17 induction independent of hypertension.

Indexed as

ADAM17 ProteinADAM ProteinsAngiotensin IIAnimalsDisease Models, AnimalEndoplasmic Reticulum StressEndothelium, VascularErbB ReceptorsErlotinib HydrochlorideHypertensionHypertrophyMiceMuscle, Smooth, VascularPhenylbutyratesQuinazolinesRandom Allocation4-phenylbutyric acidADAM17 ProteinAdam17 protein, mouseADAM ProteinsAngiotensin IIErbB ReceptorsErlotinib HydrochloridePhenylbutyratesQuinazolinesangiotensin IIfibrosishypertensionhypertrophymuscle, smooth, vascularsignal transduction

Identifiers

PMID25916723
PMCPMC4433406
OpenAlexW2164109607

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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.