Evidence map›Paper›PMID 25245389›Full record

ArticleHypertension (Dallas, Tex. : 1979)2014

CYP2J2 targeting to endothelial cells attenuates adiposity and vascular dysfunction in mice fed a high-fat diet by reprogramming adipocyte phenotype.

Nader G Abraham, Komal Sodhi, Anne M Silvis, Luca Vanella, Gaia Favero, Rita Rezzani, Craig Lee, Darryl C Zeldin, Michal L Schwartzman

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 66 citations in OpenAlex.

  1. Trial
  2. Article
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  4. Article
  5. Article
  6. Soluble Epoxide Hydrolase and Diabetes Complications.International journal of molecular sciences · 2022
    Review
  7. Article
  8. Review
  9. Article
  10. HO-1 overexpression and underexpression: Clinical implications.Archives of biochemistry and biophysics · 2019
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes.International journal of molecular sciences · 2018
    Review
  18. Article
  19. Article
  20. 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 2 countries.

Nader G AbrahamFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.). nader_abraham@nymc.edu.
Komal SodhiFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.).
Anne M SilvisFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.).
Luca VanellaFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.).
Gaia FaveroFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.).
Rita RezzaniFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.).
Craig LeeFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.).
Darryl C ZeldinFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.).
Michal L SchwartzmanFrom the Departments of Medicine and Pharmacology, New York Medical College, Valhalla (N.G.A., M.L.S.); Departments of Medicine and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV (K.S., A.M.S.); Biochemistry Section and Medicinal Chemistry Section, Department of Drug Sciences, University of Catania, Catania, Italy (L.V.); Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy (G.F., R.R.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (C.L., D.C.Z.).
University of Catania · ITUniversity of Brescia · IT

Funding

Vasoregulatory Function of CYP2E1-Derived EicosanoidsP01HL034300 · NHLBI · NEW YORK MEDICAL COLLEGE · PI JIANG, HOULI · 1985 to 2015
$33.4M
Characterization And Functional Significance Of P450 Arachidonate EpoxygenasesZIAES025034 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ZELDIN, DARRYL C · 2009 to 2025
$18.6M
HEME OXYGENASE REGULATION OF EICOSANOID BIOSYNTHESISR01DK056601 · NIDDK · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI ABRAHAM, NADER G. · 2001 to 2013
$4.4M
P450 Arachidonate EpoxygenasesZ01ES025034 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ZELDIN, DARRYL C · 1995 to 2008
$2.2M
Cytochrome P450 Derived Eicosanoids and InflammationR01GM088199 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LEE, CRAIG R · 2009 to 2013
$1.6M
Intramural NIH HHS Z01 ES025034NHLBI NIH HHS HL34300NHLBI NIH HHS HL55601NHLBI NIH HHS P01 HL034300NIDDK NIH HHS R01 DK056601NIGMS NIH HHS R01 GM088199
6 · The paper itself

Abstract

Obesity is a global epidemic and a common risk factor for endothelial dysfunction and the subsequent development of diabetes mellitus and vascular diseases such as hypertension. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP)-derived metabolites of arachidonic acid that contribute to vascular protection by stimulating vasodilation and inhibiting inflammation. Heme oxygenase-1 is a stress response protein that plays an important cytoprotective role against oxidative insult in diabetes mellitus and cardiovascular disease. We recently demonstrated interplay between EETs and heme oxygenase-1 in the attenuation of adipogenesis. We examined whether adipocyte dysfunction in mice fed a high-fat diet could be prevented by endothelial-specific targeting of the human CYP epoxygenase, CYP2J2. Tie2-CYP2J2 transgenic mice, fed a high-fat diet, had a reduction in body weight gain, blood glucose, insulin levels, and inflammatory markers. Tie2-CYP2J2 gene targeting restored HF-mediated decreases in vascular heme oxygenase-1, Cyp2C44, soluble epoxide hydrolase, phosphorylated endothelial nitric oxide synthase, phosphorylated protein kinase B, and phosphorylated adenosine monophosphate protein kinase protein expression, thus improving vascular function. These changes translated into decreased inflammation and oxidative stress within adipose tissue and decreased peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein alpha, mesoderm-specific transcript, and adipocyte 2 expression and increased uncoupling protein 1 and uncoupling protein 2 expression, reflecting the effect of vascular EET overproduction on adipogenesis. The current study documents a direct link between endothelial-specific EET production and adipogenesis, further implicating the EET-heme oxygenase-1 crosstalk as an important cytoprotective mechanism in the amelioration of vascular and adipocyte dysfunction resulting from diet-induced obesity.

Indexed as

Gene Expression RegulationAdipocytesAdiposityAnimal FeedAnimalsBlotting, WesternCytochrome P-450 CYP2J2Cytochrome P-450 Enzyme SystemDietary FatsDisease Models, AnimalDNAEndothelium, VascularImmunohistochemistryMiceMice, TransgenicObesityCYP2J2 protein, humanCytochrome P-450 CYP2J2Cytochrome P-450 Enzyme SystemDietary FatsDNA11,12-EETAMP-activated protein kinasesaP2 protein, humaneNOS protein, ratheme oxygenase-1mesoderm-specific transcript protein

Identifiers

PMID25245389
PMCPMC4230994
OpenAlexW1963705367

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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.