Evidence mapPaperPMID 39662482Full record

ArticleBritish journal of pharmacology2025

Inhibition of the upregulated phosphodiesterase 4D isoforms improves SERCA2a function in diabetic cardiomyopathy.

Zhenduo Zhu, Qiuyun Guan, Bing Xu, Sherif Bahriz, Ao Shen, Toni M West, Yu Zhang, Bingqing Deng, Wei Wei, Yongsheng Han and 2 more

Abstract read
In one paragraph

Article in British journal of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Zhenduo ZhuKey Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education; Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
Qiuyun GuanKey Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education; Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
Bing XuDepartment of Pharmacology, University of California, Davis, Davis, California, USA.
Sherif BahrizDepartment of Pharmacology, University of California, Davis, Davis, California, USA.
Ao ShenSchool of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Toni M WestDepartment of Pharmacology, University of California, Davis, Davis, California, USA.
Yu ZhangSchool of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Bingqing DengDepartment of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Wei WeiKey Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education; Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.ORCID https://orcid.org/0000-0002-3117-9598
Yongsheng HanDepartment of Emergency Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Qingtong WangKey Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education; Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.ORCID https://orcid.org/0000-0001-8249-6350
Yang K XiangDepartment of Pharmacology, University of California, Davis, Davis, California, USA.ORCID https://orcid.org/0000-0003-1786-9143

Funding

Regulation of a cardiac b1AR/SERCA2 complex in heart failureR01HL162825 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI XIANG, YANG KEVIN · 2022 to 2025
$2.5M
Molecular Regulation of cardiac adrenergic signalingR01HL147263 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI XIANG, YANG K · 2019 to 2022
$1.7M
Anhui Province Excellent Research and Innovation Team Project 2024AH010013BLRD VA I01 BX005100BLRD VA IK6 BX005753National Institute of Health grant HL147263National Institute of Health grant HL160657National Natural Science Foundation of China 81973314National Natural Science Foundation of China 82373865NHLBI NIH HHS R01 HL147263NHLBI NIH HHS R01 HL162825Postgraduate Innovation Research and Practice Program of Anhui Medical University YJS20230108VA Merit grant 01BX005100VA Merit grant IK6BX005753
6 · The paper itself

Abstract

background and purposeSarcoplasmic reticulum Ca EXPERIMENTAL APPROACH: Wild type mice were fed with either normal chow or a high-fat diet (HFD). Cardiomyocytes were isolated for excitation-contraction coupling (ECC), fluorescence resonant energy transfer PKA biosensor and proximity ligation assays. KEY

resultsThe upregulated PDE4D3 and PDE4D9 isoforms in HFD cardiomyocytes specifically bound to SERCA2a but not ryanodine receptor 2 (RyR2) on the sarcoplasmic reticulum (SR). The increased association of PDE4D isoforms with SERCA2a in HFD cardiomyocytes led to reduced local PKA activities and phosphorylation of phospholamban (PLB) but minimally effected the PKA activities and phosphorylation of RyR2. These changes correlate with slower calcium decay tau in the SR and attenuation of ECC in HFD cardiomyocytes. Selective inhibition of PDE4D3 or PDE4D9 restored PKA activities and phosphorylation of PLB at the SERCA2a complex, recovered calcium decay tau, and increased ECC in HFD cardiomyocytes. Therapies with PDE4 inhibitor roflumilast, PDE4D inhibitor BPN14770 or genetical deletion of PDE4D restored PKA phosphorylation of PLB and cardiac contractile function. CONCLUSION AND IMPLICATIONS: The current study identifies upregulation of specific PDE4D isoforms that selectively inhibit SERCA2a function in HFD-induced cardiomyopathy, indicating that this remodelling can be targeted to restore cardiac contractility in diabetic cardiomyopathy.

Indexed as

Cyclic Nucleotide Phosphodiesterases, Type 4Diabetic CardiomyopathiesPhosphodiesterase 4 InhibitorsSarcoplasmic Reticulum Calcium-Transporting ATPasesAnimalsBenzamidesCalcium-Binding ProteinsCells, CulturedCyclic AMP-Dependent Protein KinasesCyclopropanesDiet, High-FatMaleMiceMice, Inbred C57BLMyocytes, CardiacPhospholambanAtp2a2 protein, mouseBenzamidesCalcium-Binding ProteinsCyclic AMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 4CyclopropanesPDE4D protein, mousePhosphodiesterase 4 InhibitorsPhospholambanSarcoplasmic Reticulum Calcium-Transporting ATPasesdiabetic cardiomyopathyexcitation contraction couplingmyocytesPDE4DSERCA2a

Identifiers

PMID39662482
PMCPMC12225536

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.