Evidence map›Paper›PMID 41585597›Full record

ArticleEuropean heart journal open2026

Sustained HIF activation in adult cardiomyocytes show transient beneficial effect in murine HFpEF model.

Daigo Sawaki, Takayuki Isagawa, Shigeru Sato, Tatsuyuki Sato, Hiroaki Semba, Hiroki Sugimoto, Kazutoshi Ono, Ariunbold Chuluun-Erdene, Thuc Toan Pham, Ryohei Tanaka and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European heart journal open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Daigo SawakiDivision of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.ORCID https://orcid.org/0000-0003-1417-2033
Takayuki IsagawaDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Shigeru SatoDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Tatsuyuki SatoDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Hiroaki SembaDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Hiroki SugimotoDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Kazutoshi OnoDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Ariunbold Chuluun-ErdeneDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Thuc Toan PhamDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Ryohei TanakaDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Toshinaru KawakamiDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.ORCID https://orcid.org/0009-0002-7050-4514
Masamichi ItoDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Shun MinatsukiDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Yasutomi HigashikuniDivision of Cardiovascular and Genetic Research, Centre for Molecular Medicine, Jichi Medical University, Tochigi, 329-0498, Japan.ORCID https://orcid.org/0000-0002-2232-567X
Masataka AsagiriDepartment of Pharmacology, Graduate School of Medicine and RICeD, Yamaguchi University, 1-1-1 Minai-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
Ichiro ManabeDepartment of Systems Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Takahide KohroData Science Centre, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Takahiro KuchimaruDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.
Yasushi ImaiDivision of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Norihiko TakedaDivision of Cardiology and Metabolism, Centre for Molecular Medicine, 3311-1 Yakushiji, Shimotsuke, Jichi Medical University, Tochigi, 329-0498, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aims: Hypoxia-inducible factor (HIF) signalling influences cardiomyocyte differentiation, maturation, and metabolic adaptation under pathological conditions. HIF-Prolyl hydroxylase domain (HIF-PH) inhibitors, which target this pathway, have been introduced for the treatment of renal anaemia. Their precise effect or safety on cardiac function remains unclear because their pharmacokinetics and distribution are not well-understood. This study aimed to examine HIF signalling activation in adult cardiomyocytes (CMs). Methods and results: We used tamoxifen (TAM)-inducible, CM-specific von Hippel-Lindau (VHL) knockout (VHL-MCM) mice to activate CM HIF signalling. Then we subjected the mice to normal ageing or high-fat diet (HFD) and L-NAME feeding, a murine model of heart failure with preserved ejection fraction (HFpEF). In normal ageing group, there was no difference in the echocardiographic parameters or tissue fibrosis between VHL-MCM and control mice. VHL-MCM mice exhibited significantly increased capillary density and higher expression levels of HIF-target genes ( Conclusion: Sustained HIF signalling activation in adult CM does not impair the cardiac structure and function in normal ageing process and shows transient yet beneficial effect in murine HFpEF model.

Indexed as

Cardiac remodellingHeart failure with preserved ejection fraction (HFpEF)HIF-prolyl hydroxylase (HIF-PH) inhibitorsHypoxia-inducible factor 1 (HIF1)Von Hippel–Lindau (VHL) factor

Identifiers

PMID41585597
PMCPMC12825614

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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.