Evidence mapPaperPMID 40959880Full record

ArticleCirculation research2025

Dysregulated Protein

Zhen Li, Kyle B LaPenna, Natalie D Gehred, Xiaoman Yu, W H Wilson Tang, Jake E Doiron, Huijing Xia, Jingshu Chen, Ian H Driver, Frank B Sachse and 17 more

Abstract read
In one paragraph

Article in Circulation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Precision Profiling of the Cardiovascular Post-Translationally Modified Proteome.Journal of cardiovascular development and disease · 2026
    Review
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

27 authors.

Zhen LiSchool of Traditional Chinese Pharmacy (Z.L., X.Y.), China Pharmaceutical University, Nanjing, China.ORCID 0000-0002-0729-2910
Kyle B LaPennaDepartment of Pharmacology and Experimental Therapeutics, Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans (K.B.L.P., J.E.D., H.X., A.G.H.).ORCID 0000-0003-0470-0138
Natalie D GehredDepartments of Anesthesiology and Perioperative Medicine, Medicine and Physiology, Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles (N.D.G., T.G., T.M.V.).ORCID 0000-0002-7815-4881
Xiaoman YuSchool of Traditional Chinese Pharmacy (Z.L., X.Y.), China Pharmaceutical University, Nanjing, China.
W H Wilson TangDepartment of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute (W.H.W.T., A.Z.), Cleveland Clinic, OH.ORCID 0000-0002-8335-735X
Jake E DoironDepartment of Pharmacology and Experimental Therapeutics, Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans (K.B.L.P., J.E.D., H.X., A.G.H.).ORCID 0000-0002-4584-4819
Huijing XiaDepartment of Pharmacology and Experimental Therapeutics, Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans (K.B.L.P., J.E.D., H.X., A.G.H.).
Jingshu ChenGordian Biotechnology, South San Francisco, CA (J.C., I.H.D., F.B.S., N.M., M.B.J.).ORCID 0000-0002-2656-7625
Ian H DriverGordian Biotechnology, South San Francisco, CA (J.C., I.H.D., F.B.S., N.M., M.B.J.).ORCID 0000-0002-2674-5532
Frank B SachseGordian Biotechnology, South San Francisco, CA (J.C., I.H.D., F.B.S., N.M., M.B.J.).ORCID 0000-0003-4987-705X
Naoto MuraokaGordian Biotechnology, South San Francisco, CA (J.C., I.H.D., F.B.S., N.M., M.B.J.).ORCID 0000-0003-0057-0292
Antonia KatsoudaLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece (A.K., P.Z., A.P.).ORCID 0000-0002-3253-2250
Paraskevas ZampasLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece (A.K., P.Z., A.P.).ORCID 0009-0009-2984-311X
Amelia G HaydelDepartment of Pharmacology and Experimental Therapeutics, Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans (K.B.L.P., J.E.D., H.X., A.G.H.).
Heather QuiriarteVascular Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA (H.Q., T.D.A.).
Timothy D AllertonVascular Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA (H.Q., T.D.A.).ORCID 0000-0001-6364-5787
Alexia ZagourasDepartment of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute (W.H.W.T., A.Z.), Cleveland Clinic, OH.
Jennifer WilcoxDepartment of Cardiovascular and Metabolic Sciences, Center of Microbiome and Human Health (W.H.W.T., A.Z., J.W.), Cleveland Clinic, OH.ORCID 0000-0001-6277-1079
Tatiana GromovaDepartments of Anesthesiology and Perioperative Medicine, Medicine and Physiology, Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles (N.D.G., T.G., T.M.V.).ORCID 0000-0001-5597-2067
Yueqin ZhengState Key Laboratory of Natural Medicine, Center of Drug Discovery (Y.Z.), China Pharmaceutical University, Nanjing, China.
Andreas PapapetropoulosLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece (A.K., P.Z., A.P.).ORCID 0000-0002-4253-5930
Sanjiv J ShahNorthwestern University Medicine, Feinberg School of Medicine, Chicago, IL (S.J.S.).ORCID 0000-0002-5655-8201
Traci T GoodchildDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (Z.L., X.Y., T.T.G., D.J.L.).
Martin B JensenGordian Biotechnology, South San Francisco, CA (J.C., I.H.D., F.B.S., N.M., M.B.J.).ORCID 0000-0002-8875-0345
Thomas E SharpDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL (T.E.S.).ORCID 0000-0001-8706-9825
Thomas M VondriskaDepartments of Anesthesiology and Perioperative Medicine, Medicine and Physiology, Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles (N.D.G., T.G., T.M.V.).ORCID 0009-0000-5238-1245
David J LeferDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (Z.L., X.Y., T.T.G., D.J.L.).ORCID 0000-0003-2293-7278

Funding

The role of maternal obesity-driven inflammation and adverse pregnancy outcomes in a mouse model of preeclampsiaP20GM135002 · NIGMS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2022 to 2025
$6.5M
Louisiana Clinical and Translational Science CenterU54GM104940 · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2025 to 2025
$3.9M
Pilot and Feasibility ProgramP30DK072476 · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2005 to 2025
$2.2M
Roles of Endothelial and Smooth Muscle KATP Channels in Myocardial Ischemic InjuryR01HL146514 · NHLBI · LSU HEALTH SCIENCES CENTER · PI William A Coetzee, DAVID JOSEPH LEFER · 2021 to 2022
$1.5M
Hydrogen Sulfide and GLP-1 Combination Therapy to Treat HFpEFR01HL181016 · CEDARS-SINAI MEDICAL CENTER · 2025 to 2025
$759k
Regulation of gene transcription and alternative splicing by a long non-coding RNAR01HL159086 · UNIVERSITY OF SOUTH FLORIDA · 2025 to 2025
$506k
Alcohol-induced Gut Dysbiosis and Cardiovascular DiseaseR01AA029984 · UNIVERSITY OF SOUTH FLORIDA · 2025 to 2025
$412k
Endogenous Hydrogen Sulfide Enzymes in Heart FailureR01HL146098 · NHLBI · LSU HEALTH SCIENCES CENTER · PI Huijing Xia · 2022 to 2022
$401k
Dynamics of cardiac nuclei in heart diseaseR01HL105699 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$390k
NCATS NIH HHS TL1 TR003106NHLBI NIH HHS R01 HL105699NHLBI NIH HHS R01 HL146098NHLBI NIH HHS R01 HL146514NHLBI NIH HHS R01 HL151398NHLBI NIH HHS R01 HL159086NHLBI NIH HHS R01 HL159428NHLBI NIH HHS R01 HL181016NIAAA NIH HHS R01 AA029984NIDDK NIH HHS P30 DK072476NIGMS NIH HHS P20 GM103528NIGMS NIH HHS P20 GM135002NIGMS NIH HHS U54 GM104940
6 · The paper itself

Abstract

backgroundRecent studies suggest aberrant elevation of iNOS (inducible NO synthase) expression and excessive protein

methodsCirculating nitrite (NO bioavailability) and nitrosothiols were quantified in patients with HFpEF. Parallel studies using rodent models of cardiometabolic HFpEF were performed to evaluate cardiac function, NO signaling, and total nitroso species during disease progression. Single-nucleus RNA sequencing and proteomic analysis were conducted to identify regulatory genes and cellular targets of pathological

resultsIn patients with HFpEF, circulating nitrosothiols were significantly elevated, indicating heightened nitrosative stress, whereas nitrite levels remained unchanged. In ZSF1 Obese (ob) rats, NO bioavailability declined with age, whereas total nitroso species progressively increased as HFpEF worsened. Transcriptomic analysis revealed marked upregulation of a transnitrosylase HBb (hemoglobin-β subunit), validated in both rat and human HFpEF hearts. Enzymatic assays demonstrated aberrant functions of Trx2 (thioredoxin 2) and GSNOR (S-nitrosoglutathione reductase) in ZSF1 Ob hearts. Cell-based experiments confirmed that altered expression or function of HBb, Trx2, and GSNOR resulted in elevated cellular RxNO. Additionally, similar dysregulation of

conclusionsThese data demonstrate that nitrosative stress, evidenced by dysregulated protein

Indexed as

Heart FailureNitrosative StressStroke VolumeAgedAldehyde OxidoreductasesAnimalsDisease Models, AnimalDisease ProgressionFemaleHumansMaleMiddle AgedNitric OxideNitric Oxide Synthase Type IIRatsRats, ZuckerAldehyde OxidoreductasesNitric OxideNitric Oxide Synthase Type IIbeta-globinsheart failureheart failure, diastolichemoglobinsnitric oxidenitrosative stressprotein processing, post-translational

Identifiers

PMID40959880
PMCPMC12908239

What Socratic holds

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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 Socratic graph.