Evidence map›Paper›PMID 29295852›Full record

ArticleHypertension (Dallas, Tex. : 1979)2018

Cyclooxygenase-2 Selectively Controls Renal Blood Flow Through a Novel PPARβ/δ-Dependent Vasodilator Pathway.

Nicholas S Kirkby, Walkyria Sampaio, Gisele Etelvino, Daniele T Alves, Katie L Anders, Rafael Temponi, Fisnik Shala, Anitha S Nair, Blerina Ahmetaj-Shala, Jing Jiao and 5 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

21 citing papers in PubMed, 39 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 4 countries.

Nicholas S KirkbyFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.). n.kirkby@imperial.ac.uk j.a.mitchell@ic.ac.uk.
Walkyria SampaioFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Gisele EtelvinoFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Daniele T AlvesFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Katie L AndersFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Rafael TemponiFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Fisnik ShalaFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Anitha S NairFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Blerina Ahmetaj-ShalaFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Jing JiaoFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Harvey R HerschmanFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Xiaomeng WangFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Walter WahliFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Robson A SantosFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.).
Jane A MitchellFrom the Vascular Biology, National Heart and Lung Institute, Imperial College London, United Kingdom (N.S.K., K.L.A., F.S., A.S.N., B.A.-S., J.A.M.); Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil (W.S., G.E., D.T.A., R.T., R.A.S.); Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (J.J., H.R.H.); Vascular Biology Laboratory, Lee Kong Chian School of Medicine (W.X.) and Lee Kong Chian School of Medicine (W.W), Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Proteos, Agency for Science Technology and Research, Singapore, Singapore (W.X.); Department of Cell Biology, Institute of Ophthalmology, University College London, United Kingdom (W.X.); Singapore Eye Research Institute (W.X.); and Center for Integrative Genomics, University of Lausanne, Switzerland (W.W.). n.kirkby@imperial.ac.uk j.a.mitchell@ic.ac.uk.
University College London · GBUniversity of California, Los Angeles · USInstitute of Molecular and Cell Biology · SGNanyang Technological University · SGSingapore Eye Research Institute · SGUniversidade Federal de Minas Gerais · BRAgency for Science, Technology and Research · SG

Funding

British Heart Foundation FS/16/1/31699British Heart Foundation PG/16/83/32467Wellcome Trust 085255
6 · The paper itself

Abstract

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in inflammation and cancer targeted by nonsteroidal anti-inflammatory drugs. COX-2 is also expressed constitutively in discreet locations where its inhibition drives gastrointestinal and cardiovascular/renal side effects. Constitutive COX-2 expression in the kidney regulates renal function and blood flow; however, the global relevance of the kidney versus other tissues to COX-2-dependent blood flow regulation is not known. Here, we used a microsphere deposition technique and pharmacological COX-2 inhibition to map the contribution of COX-2 to regional blood flow in mice and compared this to COX-2 expression patterns using luciferase reporter mice. Across all tissues studied, COX-2 inhibition altered blood flow predominantly in the kidney, with some effects also seen in the spleen, adipose, and testes. Of these sites, only the kidney displayed appreciable local COX-2 expression. As the main site where COX-2 regulates blood flow, we next analyzed the pathways involved in kidney vascular responses using a novel technique of video imaging small arteries in living tissue slices. We found that the protective effect of COX-2 on renal vascular function was associated with prostacyclin signaling through PPARβ/δ (peroxisome proliferator-activated receptor-β/δ). These data demonstrate the kidney as the principle site in the body where local COX-2 controls blood flow and identifies a previously unreported PPARβ/δ-mediated renal vasodilator pathway as the mechanism. These findings have direct relevance to the renal and cardiovascular side effects of drugs that inhibit COX-2, as well as the potential of the COX-2/prostacyclin/PPARβ/δ axis as a therapeutic target in renal disease.

Indexed as

AnimalsCyclooxygenase 2Cyclooxygenase InhibitorsKidneyMicePPAR-betaPPAR deltaRenal CirculationSignal TransductionCyclooxygenase 2Cyclooxygenase InhibitorsPPAR-betaPPAR deltacyclooxygenase 2endotheliuminflammationregional blood flowspleen

Identifiers

PMID29295852
PMCPMC5770101
OpenAlexW2782425343

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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.