Evidence map›Paper›PMID 26602865›Full record

ArticleCirculation research2016

Uncoupling Caveolae From Intracellular Signaling In Vivo.

Jan R Kraehling, Zhengrong Hao, Monica Y Lee, David J Vinyard, Heino Velazquez, Xinran Liu, Radu V Stan, Gary W Brudvig, William C Sessa

Abstract read
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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.5field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Stimulation of Caveolin-1 Signaling Improves Arteriovenous Fistula Patency.Arteriosclerosis, thrombosis, and vascular biology · 2019
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Caveolins and caveolae in ocular physiology and pathophysiology.Progress in retinal and eye research · 2017
    Review
  15. Article
  16. Article
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 2 institutions in 1 country.

Jan R KraehlingFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
Zhengrong HaoFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
Monica Y LeeFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
David J VinyardFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
Heino VelazquezFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
Xinran LiuFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
Radu V StanFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
Gary W BrudvigFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
William C SessaFrom the Vascular Biology and Therapeutics Program (J.R.K., Z.H., M.Y.L., W.C.S.) and Department of Pharmacology (J.R.K., Z.H., M.Y.L., W.C.S.), Yale University School of Medicine, New Haven, CT; Department of Chemistry, Yale University, New Haven, CT (D.J.V., G.W.B.); Department of Internal Medicine, VA Connecticut Healthcare System, West Haven, CT (H.V.); Department of Cell Biology, Yale University, School of Medicine, New Haven, CT (X.L.); and Department of Pathology, Dartmouth Medical School, Lebanon, NH (R.V.S.).
VA Connecticut Healthcare System · USYale University · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
Renal Physiology and Phenotyping CoreP30DK079310 · NIDDK · YALE UNIVERSITY · PI SOMLO, STEFAN · 2008 to 2022
$16.8M
PHOSPHORYLATION AND ENDOTHELIAL NITRIC OXIDE PRODUCTIONR01HL064793 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2000 to 2016
$6.3M
Endothelial NOS by protein to protein interactionsR37HL061371 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2009 to 2017
$4.1M
Regulation of vascular remodeling &angiogenesis by NogoR01HL081190 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2005 to 2014
$4.1M
Endothelial NOS by Protein-Protein IntractionsR01HL061371 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 1999 to 2008
$3.6M
Vascular Remodeling: Role of Nitric OxideR01HL057665 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C. · 1996 to 2004
$1.5M
NgBR as a regulator of endothelial functionR01HL133018 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2016 to 2017
$995k
An isoform-specific, conditional deletion approach to decipher Akt1 and Akt2 funcF32HL119147 · NHLBI · YALE UNIVERSITY · PI LEE, MONICA Y · 2013 to 2015
$159k
NCI NIH HHS P30 CA023108NHLBI NIH HHS F32 HL119147NHLBI NIH HHS P01 HL1070295NHLBI NIH HHS R01 HL057665NHLBI NIH HHS R01 HL061371NHLBI NIH HHS R01 HL064793NHLBI NIH HHS R01 HL081190NHLBI NIH HHS R01 HL133018NHLBI NIH HHS R01 HL61371NHLBI NIH HHS R01 HL64793NHLBI NIH HHS R37 HL061371NIDDK NIH HHS P30 DK079310
6 · The paper itself

Abstract

rationaleCaveolin-1 (Cav-1) negatively regulates endothelial nitric oxide (NO) synthase-derived NO production, and this has been mapped to several residues on Cav-1, including F92. Herein, we reasoned that endothelial expression of an F92ACav-1 transgene would let us decipher the mechanisms and relationships between caveolae structure and intracellular signaling.

objectiveThis study was designed to separate caveolae formation from its downstream signaling effects. METHODS AND

resultsAn endothelial-specific doxycycline-regulated mouse model for the expression of Cav-1-F92A was developed. Blood pressure by telemetry and nitric oxide bioavailability by electron paramagnetic resonance and phosphorylation of vasodilator-stimulated phosphoprotein were determined. Caveolae integrity in the presence of Cav-1-F92A was measured by stabilization of caveolin-2, sucrose gradient, and electron microscopy. Histological analysis of heart and lung, echocardiography, and signaling were performed.

conclusionsThis study shows that mutant Cav-1-F92A forms caveolae structures similar to WT but leads to increases in NO bioavailability in vivo, thereby demonstrating that caveolae formation and downstream signaling events occur through independent mechanisms.

Indexed as

AnimalsBlood PressureCaveolaeCaveolin 1DoxycyclineHumansIntracellular FluidMaleMiceMice, Inbred C57BLMice, TransgenicNitric OxideSignal TransductionUncoupling AgentsCav1 protein, mouseCaveolin 1DoxycyclineNitric OxideUncoupling Agentscaveolin-1cell endothelial celleNOSmicenitric oxidevascular function

Identifiers

PMID26602865
PMCPMC4740205
OpenAlexW2179431905

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.