Evidence map›Paper›PMID 40797115›Full record

ArticleActa pharmacologica Sinica2026

Inhibition of Setd7 protects against cardiomyocyte hypertrophy via inhibiting lipid oxidation.

Hai-Bi Su, Jing-Huan Wang, Yu-Yu Zhang, Jie Xu, Jia-Yao Liu, Yu-Hui Li, Chen-Xi Xiao, Cai-Yun Wang, Jun Chang, Xin-Hua Liu

Abstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

10 authors.

Hai-Bi Su *Phenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China.
Jing-Huan Wang *Phenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China.
Yu-Yu Zhang *Phenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China.
Jie XuPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China.
Jia-Yao LiuPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China.
Yu-Hui LiPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China.
Chen-Xi XiaoPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China.
Cai-Yun WangPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China.
Jun ChangPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China. jchang@fudan.edu.cn.
Xin-Hua LiuPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 200120, China. liuxinhua@fudan.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myocardial hypertrophy is one of the most prominent features of heart failure. SET domain-containing protein 7 (Setd7), a catalytic enzyme responsible for histone H3K4 methylation, has been implicated in various cardiac diseases. In this study we investigated whether Setd7 contributed to the development of cardiac hypertrophy. Male mice were subjected to a hypobaric hypoxic environment for 8 weeks; neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia for 6 h. We showed that hypoxic stimulation significantly upregulated the expression levels of Setd7 along with the expression of hypertrophic markers ANP and BNP in NRCMs. By conducting loss- and gain-of-function assays, we demonstrated that Setd7 modulated the hypertrophic and inflammatory markers in hypoxic cardiomyocytes. We further revealed that Setd7-mediated activation of E2F1 (E2 promoter binding factor 1) triggered the expression of E3 ubiquitin protein ligases WWP2, which catalyzed the ubiquitination and degradation of glutathione peroxidase 4 (GPx4), a critical lipid peroxide-reducing enzyme. This degradation drove extensive lipid peroxidation, thereby exacerbating pathological cardiac hypertrophy. Notably, GPx4 inhibition by ras-selective lethal small molecule 3 (RSL3) abolished the antihypertrophic effects of Setd7 knockdown in cardiomyocytes, underscoring the pivotal role of lipid peroxidation in Setd7-mediated hypertrophic responses. In summary, Setd7 promotes hypoxia-induced cardiac hypertrophy through the Setd7-E2F1-WWP2-GPx4 signaling pathway, suggesting that targeting Setd7 is a promising therapeutic strategy to alleviate hypoxia-induced myocardial hypertrophy.

Indexed as

CardiomegalyHistone-Lysine N-MethyltransferaseLipid PeroxidationMyocytes, CardiacAnimalsCells, CulturedMaleMiceMice, Inbred C57BLOxidation-ReductionRatsRats, Sprague-DawleyHistone-Lysine N-MethyltransferaseSetd7 protein, mousecardiomyocytes hypertrophyGPx4hypoxialipid peroxidationRSL3Setd7

Identifiers

PMID40797115
PMCPMC12811361

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.