Evidence mapPaperPMID 41540467Full record

ArticleStem cell research & therapy2026

FHOD3 deficiency disrupts sarcomere organization and activates caMKII signaling in human stem cell-derived cardiomyocytes.

Mingyu Wei, Xiaojie Hou, Siyao Zhang, Xianjing Hu, Xi Chen, Zhen Gao, Shuwan Xu, Zhan Shi, Min Zhu, Feng Lan and 1 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2026. 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

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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. Intracellular Ionic Remodeling During Fetal Development of Hereditary Cardiomyopathy of the Hamster.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Article
4 · The record

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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

11 authors.

Mingyu Wei *Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100037, China.
Xiaojie Hou *Department of Cardiovascular Surgery, Institute of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Siyao Zhang *Maternal-Fetal Medicine Center in Fetal Heart Disease, Capital Medical University, Beijing Anzhen Hospital, Beijing, 100029, China.
Xianjing HuNursing Department, Peking University Third Hospital, Beijing, China.
Xi ChenDepartment of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100037, China.
Zhen GaoDepartment of Kidney Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, China.
Shuwan XuDepartment of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100037, China.
Zhan ShiDepartment of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100037, China.
Min ZhuState Key Laboratory of Cardiovascular Disease, Key Laboratory of Pluripotent Stem Cells in Cardiac Repair and Regeneration, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China. zhumin1013@163.com.
Feng LanState Key Laboratory of Cardiovascular Disease, Key Laboratory of Pluripotent Stem Cells in Cardiac Repair and Regeneration, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China. fenglan@ccmu.edu.cn.
Ming CuiDepartment of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100037, China. mingcui@bjmu.edu.cn.

Funding

National Natural Science Foundation of China 82070272The Beijing Research Ward Excellence Clinical Study Program BRWEP2024W014090201
6 · The paper itself

Abstract

backgroundInherited cardiomyopathy (ICM) is a genetic disorder characterized by abnormal myocardial structure and function, often progressing to heart failure. FHOD3, a member of the Formin gene family, plays a crucial role in cardiomyocyte cytoskeletal organization. Mutations in FHOD3 have been associated with various cardiomyopathies, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and left ventricular noncompaction (LVNC). However, the molecular mechanisms underlying FHOD3 deficiency-induced cardiomyopathy remain elusive.

methodsA FHOD3 knockout (FHOD3

resultsFHOD3-deficient hESC-CMs exhibited marked sarcomere disorganization and degradation, impaired calcium handling and compromised mitochondrial function, ultimately leading to reduced contractility. Transcriptomic analysis revealed significant downregulation of sarcomere-related genes and calcium-handling genes, with enrichment in pathways associated with cardiomyopathy and calcium signaling. Furthermore, FHOD3 deficiency triggered the phosphorylation of CaMKII (Thr286), a key regulator of cardiac hypertrophy and remodeling, contributing to the progression of heart failure. Treatment with the myosin activator Omecamtiv mecarbil (OM) partially restored contractility without affecting calcium handling, highlighting its potential as a therapeutic strategy.

conclusionsOur study establishes a valuable human-derived model for investigating the molecular mechanisms of FHOD3 deficiency-induced cardiomyopathy. This model allows for extensive investigation into the phenotypes caused by FHOD3 deficiency and identifies CaMKII activation as a crucial factor contributing to the HF phenotype. Additionally, this model serves as an important tool for discovering novel therapeutic agents, and we demonstrate that OM can partially improve myocardial function in FHOD3 KO hESC-CMs.

Indexed as

Calcium-Calmodulin-Dependent Protein Kinase Type 2Human Embryonic Stem CellsMyocytes, CardiacSarcomeresCalciumCell DifferentiationCell LineForminsHumansSignal TransductionCalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2FHOD3 protein, humanForminsCaMKII activationCardiomyopathyCRISPR/Cas9FHOD3Human embryonic stem cell

Identifiers

PMID41540467
PMCPMC12892442

What Socratic holds

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LicenceCC BY-NC-ND
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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.