ArticleJCI insight2019
Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays disease onset.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
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.
Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Mechanical stiffness orchestrates distinct regulation of MRTFs and YAP/TAZ transcriptional cofactors in hepatocytes.The FEBS journal · 2026Article
- "Double-hit" precipitates fulminant cardiac dysfunction in a child with homozygous CAP2 variant: a case report.Frontiers in cardiovascular medicine · 2026Article
- Cyclase-associated protein (CAP) inhibits inverted formin 2 (INF2) to induce dendritic spine maturation.Cellular and molecular life sciences : CMLS · 2024Article
- Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease.EMBO molecular medicine · 2023Article
- SRF: a seriously responsible factor in cardiac development and disease.Journal of biomedical science · 2022Review
- Redefining actin dynamics of the pointed-end complex in striated muscle.Trends in cell biology · 2021Article
- Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons.Cells · 2021Article
- Cyclase-associated protein 2 (CAP2) controls MRTF-A localization and SRF activity in mouse embryonic fibroblasts.Scientific reports · 2021Article
- Molecular Mechanisms of Leukocyte Migration and Its Potential Targeting-Lessons Learned From MKL1/SRF-Related Primary Immunodeficiency Diseases.Frontiers in immunology · 2021Review
- Molecular Signatures and Networks of Cardiomyocyte Differentiation in Humans and Mice.Molecular therapy. Nucleic acids · 2020Article
- A Critical Role for Estrogen-Related Receptor Signaling in Cardiac Maturation.Circulation research · 2020Article
- CAPt'n of Actin Dynamics: Recent Advances in the Molecular, Developmental and Physiological Functions of Cyclase-Associated Protein (CAP).Frontiers in cell and developmental biology · 2020Review
- An MRTF-A-Sp1-PDE5 Axis Mediates Angiotensin-II-Induced Cardiomyocyte Hypertrophy.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
About one-third of dilated cardiomyopathy (DCM) cases are caused by mutations in sarcomere or cytoskeletal proteins. However, treating the cytoskeleton directly is not possible because drugs that bind to actin are not well tolerated. Mutations in the actin binding protein CAP2 can cause DCM and KO mice, either whole body (CAP2-KO) or cardiomyocyte-specific KOs (CAP2-CKO) develop DCM with cardiac conduction disease. RNA sequencing analysis of CAP2-KO hearts and isolated cardiomyocytes revealed overactivation of fetal genes, including serum response factor-regulated (SRF-regulated) genes such as Myl9 and Acta2 prior to the emergence of cardiac disease. To test if we could treat CAP2-KO mice, we synthesized and tested the SRF inhibitor CCG-1423-8u. CCG-1423-8u reduced expression of the SRF targets Myl9 and Acta2, as well as the biomarker of heart failure, Nppa. The median survival of CAP2-CKO mice was 98 days, while CCG-1423-8u-treated CKO mice survived for 116 days and also maintained normal cardiac function longer. These results suggest that some forms of sudden cardiac death and cardiac conduction disease are under cytoskeletal stress and that inhibiting signaling through SRF may benefit DCM by reducing cytoskeletal stress.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.