ReviewBiophysical reviews2018
Four and a half LIM domain protein signaling and cardiomyopathy.
Review in Biophysical reviews, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Clinical spectrum, cardiac phenotypes, and outcomes of FHL1-related cardiomyopathies: a systematic review.BMC cardiovascular disorders · 2026Pooled it
- Integrative transcriptomic, proteomic, and machine learning approach to identifying feature genes of atrial fibrillation using atrial samples from patients with valvular heart disease.BMC cardiovascular disorders · 2021Pooled it
- Mitochondrial flagella-like extensions (MitoFLARE) dysfunction triggers STING-mediated immune dysregulation in sepsis.Nature communications · 2026Article
- Sotagliflozin Enhances Left Ventricular Function and Myocardial Perfusion in Chronic Myocardial Ischemia Through Metabolic and Redox Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- A titin missense variant drives atrial electrical remodeling and is associated with atrial fibrillation.eLife · 2026Article
- Identification of MTURN as a trained immunity-related biomarker for heart failureFrontiers in immunology · 2026Article
- Long-Term Impact of Western Diet on Right Ventricular Transcriptome: Uncovering Sex-Specific Patterns in C57BL/6J Mice.International journal of molecular sciences · 2025Article
- A titin missense variant drives atrial electrical remodeling and is associated with atrial fibrillation.medRxiv : the preprint server for health sciences · 2025Article
- Unlocking the secrets of Cardiac development and function: the critical role of FHL2.Molecular and cellular biochemistry · 2025Review
- FHL2 in arterial medial calcification in chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Structural domain in the Titin N2B-us region binds to FHL2 in a force-activation dependent manner.Nature communications · 2024Article
- Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies.Scientific reports · 2024Review
- The roles of FHL2 in cancer.Clinical and experimental medicine · 2023Review
- Characterization of a robust mouse model of heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2023Article
- Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L.PNAS nexus · 2023Article
- FHL2 Genetic Polymorphisms and Pro-Diabetogenic Lipid Profile in the Multiethnic HELIUS Cohort.International journal of molecular sciences · 2023Article
- Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy.Journal of molecular and cellular cardiology · 2023Article
- Insulin and Insulin-Like Growth Factor 1 Signaling Preserves Sarcomere Integrity in the Adult Heart.Molecular and cellular biology · 2022Article
- SRF: a seriously responsible factor in cardiac development and disease.Journal of biomedical science · 2022Review
- Pediatric Hypertrophic Cardiomyopathy: Exploring the Genotype-Phenotype Association.Journal of the American Heart Association · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Four and a half LIM domain (FHL) protein family members, FHL1 and FHL2, are multifunctional proteins that are enriched in cardiac muscle. Although they both localize within the cardiomyocyte sarcomere (titin N2B), they have been shown to have important yet unique functions within the context of cardiac hypertrophy and disease. Studies in FHL1-deficient mice have primarily uncovered mitogen-activated protein kinase (MAPK) scaffolding functions for FHL1 as part of a novel biomechanical stretch sensor within the cardiomyocyte sarcomere, which acts as a positive regulator of pressure overload-mediated cardiac hypertrophy. New data have highlighted a novel role for the serine/threonine protein phosphatase (PP5) as a deactivator of the FHL1-based biomechanical stretch sensor, which has implications in not only cardiac hypertrophy but also heart failure. In contrast, studies in FHL2-deficient mice have primarily uncovered an opposing role for FHL2 as a negative regulator of adrenergic-mediated signaling and cardiac hypertrophy, further suggesting unique functions targeted by FHL proteins in the "stressed" cardiomyocyte. In this review, we provide current knowledge of the role of FHL1 and FHL2 in cardiac muscle as it relates to their actions in cardiac hypertrophy and cardiomyopathy. A specific focus will be to dissect the pathways and protein-protein interactions that underlie FHLs' signaling role in cardiac hypertrophy as well as provide a comprehensive list of FHL mutations linked to cardiac disease, using evidence gained from genetic mouse models and human genetic studies.
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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.