Evidence map›Paper›PMID 25489061›Full record

ArticleHypertension (Dallas, Tex. : 1979)2015

Uric acid promotes left ventricular diastolic dysfunction in mice fed a Western diet.

Guanghong Jia, Javad Habibi, Brian P Bostick, Lixin Ma, Vincent G DeMarco, Annayya R Aroor, Melvin R Hayden, Adam T Whaley-Connell, James R Sowers

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
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. It is linked to trial NCT03700645 (Allopurinol in the Treatment of Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease Treated by Either PCI or CABG), which is not on this map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
7.0field-weighted citation impact, top 2% 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.

NCT03700645 phase4unknown statusnot on this mapstarted 2018, after this paper: background citation

Allopurinol in the Treatment of Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease Treated by Either PCI or CABG: Pilot Study

TypeinterventionalSponsorTel-Aviv Sourasky Medical CenterRan2018 to 2020Enrolled100ConditionsDiabetes Mellitus, Ischemic Heart Disease, Multi Vessel Coronary Artery DiseaseArmsAllopurinol
3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 140 citations in OpenAlex.

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  12. Obesity-Associated Hyperuricemia in Female Mice: A Reevaluation.Gout, urate, and crystal deposition disease · 2024
    Article
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22 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

9 authors at 1 institution in 1 country.

Guanghong JiaFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.).
Javad HabibiFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.).
Brian P BostickFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.).
Lixin MaFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.).
Vincent G DeMarcoFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.).
Annayya R AroorFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.).
Melvin R HaydenFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.).
Adam T Whaley-ConnellFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.).
James R SowersFrom the Division of Endocrinology and Metabolism, Department of Medicine (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), Division of Nephrology and Hypertension, Department of Medicine (A.T.W.-C.), Department of Medical Pharmacology and Physiology (V.G.D., J.R.S.), Diabetes and Cardiovascular Center (G.J., J.H., B.P.B., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.), and Department of Radiology (L.M.), University of Missouri School of Medicine, Columbia; and Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO (G.J., J.H., B.P.B., L.M., V.G.D., A.R.A., M.R.H., A.T.W.-C., J.R.S.). sowersj@health.missouri.edu.
Jisc · GB

Funding

ANG II OPPOSES INS MEDIATED VASORELAXATION &GLU UTILZAR01HL073101 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI SOWERS, JAMES RUSSELL · 2004 to 2013
$2.7M
Ang II and Overnutrition and Insulin resistance in Cardiovascular TissueR01HL107910 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI SOWERS, JAMES RUSSELL · 2011 to 2015
$1.8M
Interactions of the RAAS and a Western Diet on Insulin Metabolic ActionsI01BX001981 · VA · HARRY S. TRUMAN MEMORIAL VA HOSPITAL · PI LASTRA, GUIDO · 2013 to 2022
–
BLRD VA I01 BX001981NHLBI NIH HHS R01 HL073101NHLBI NIH HHS R01 HL107910NHLBI NIH HHS R01 HL107910-01NHLBI NIH HHS R01 HL73101-01A
6 · The paper itself

Abstract

The rising obesity rates parallel increased consumption of a Western diet, high in fat and fructose, which is associated with increased uric acid. Population-based data support that elevated serum uric acids are associated with left ventricular hypertrophy and diastolic dysfunction. However, the mechanism by which excess uric acid promotes these maladaptive cardiac effects has not been explored. In assessing the role of Western diet-induced increases in uric acid, we hypothesized that reductions in uric acid would prevent Western diet-induced development of cardiomyocyte hypertrophy, cardiac stiffness, and impaired diastolic relaxation by reducing growth and profibrotic signaling pathways. Four-weeks-old C57BL6/J male mice were fed excess fat (46%) and fructose (17.5%) with or without allopurinol (125 mg/L), a xanthine oxidase inhibitor, for 16 weeks. The Western diet-induced increases in serum uric acid along with increases in cardiac tissue xanthine oxidase activity temporally related to increases in body weight, fat mass, and insulin resistance without changes in blood pressure. The Western diet induced cardiomyocte hypertrophy, myocardial oxidative stress, interstitial fibrosis, and impaired diastolic relaxation. Further, the Western diet enhanced activation of the S6 kinase-1 growth pathway and the profibrotic transforming growth factor-β1/Smad2/3 signaling pathway and macrophage proinflammatory polarization. All results improved with allopurinol treatment, which lowered cardiac xanthine oxidase as well as serum uric acid levels. These findings support the notion that increased production of uric acid with intake of a Western diet promotes cardiomyocyte hypertrophy, inflammation, and oxidative stress that lead to myocardial fibrosis and associated impaired diastolic relaxation.

Indexed as

AllopurinolAnimalsBiomarkersDietary FatsDietary SucroseDiet, WesternDisease Models, AnimalFibrosisHypertrophy, Left VentricularMaleMiceMice, Inbred C57BLMyocardiumOxidative StressSignal TransductionUric AcidAllopurinolBiomarkersDietary FatsDietary SucroseUric AcidXanthine Oxidase

Identifiers

PMID25489061
PMCPMC4370431
OpenAlexW2148684611

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Registered trials

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.