Evidence map›Paper›PMID 40770599›Full record

ArticleInflammation2025

Membrane-Associated RING-CH-Type Finger 6 Protects against Hypertension-Induced Cardiac Remodeling by Suppressing Cardiomyocyte Ferroptosis Through the Degradation of ACSL4.

Rui Hao, Xin Wang, Changhu Liu, Jianghua Xue

Abstract read
In one paragraph

Article in Inflammation, 2025. 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

4 authors.

Rui HaoDepartment of Cardiology and Hypertension, Central Hospital Affiliated to Shandong First Medical University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China.
Xin WangComprehensive Vascular Disease Management Center, Central Hospital, Shandong First Medical University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China.
Changhu LiuDepartment of Health Care and Geriatrics, Central Hospital Affiliated to Shandong First Medical University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China.
Jianghua XueDepartment of Cardiology, Central Hospital Affiliated to Shandong First Medical University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China. xuejianghua_xjh@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypertension serves as a major contributing factor to various cardiovascular disorders, including heart failure. Ferroptosis-induced cardiomyocyte loss is recognized as a novel contributor to myocardial remodeling in heart failure. Membrane-associated RING-CH-type finger 6 (Marchf6) is a newly identified gene that regulates ferroptosis and is implicated in various disease processes. However, the role of Marchf6 in modulating cardiomyocyte ferroptosis and its impact on hypertension-induced myocardial remodeling remain unexplored. This study aimed to investigate whether Marchf6 influences myocardial remodeling through the regulation of ferroptosis and to explore the underlying molecular mechanisms. Our findings indicated that there was a decrease in Marchf6 levels in both animal and cellular models established through Angiotensin II (Ang II) stimulation. Overexpression of Marchf6 conferred resistance to Erastin-induced ferroptosis, while Marchf6 knockdown increased sensitivity to ferroptosis. In the Ang II cellular model, Marchf6 overexpression enhanced cell viability, inhibited cardiomyocyte hypertrophy, and reversed ferroptosis-related indicators, whereas Marchf6 knockdown exhibited opposite effects. Animal model studies indicated that Marchf6 overexpression significantly improved cardiac function, alleviated myocardial hypertrophy and fibrosis, and suppressed ferroptotic death levels. Mechanistic investigations revealed that Marchf6 significantly regulated the stability of ACSL4 protein, with Marchf6 overexpression accelerating ACSL4 protein degradation. In cardiomyocytes overexpressing Marchf6, ACSL4 overexpression notably reversed the regulatory impact of Marchf6 on cardiac cell hypertrophy and ferroptosis triggered by Ang II. Collectively, our findings suggest that Marchf6 may mitigate cardiomyocyte ferroptosis by promoting ACSL4 degradation, thereby alleviating hypertension-induced myocardial remodeling. This study not only uncovers a novel regulatory mechanism of cardiomyocyte ferroptosis in myocardial remodeling but also presents a viable target for the management of hypertension-related cardiac diseases.

Indexed as

Coenzyme A LigasesFerroptosisHypertensionMembrane ProteinsMyocytes, CardiacVentricular RemodelingAngiotensin IIAnimalsLong-Chain-Fatty-Acid-CoA LigaseMaleMiceRatsAcsl4 protein, mouseAngiotensin IICoenzyme A LigasesLong-Chain-Fatty-Acid-CoA LigaseMembrane ProteinsACSL4Cardiac remodelingFerroptosisHypertensionMarchf6

Identifiers

PMID40770599
PMCPMC12722403

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.