Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22

Prestes, Priscilla; Marques, Francine Z.; López–Campos, Guillermo; Booth, Scott A.; McGlynn, Maree A; Lewandowski, Paul; Delbridge, L.; Harrap, Stephen; Charchar, Fadi J.

doi:10.1097/hjh.0000000000000875

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…DNA sequence variants in HHR were identified according to methods detailed previously (30). Briefly, we sequenced the whole genome of 1 male 13-wk-old NHR and 1 age-matched HHR.…”

Section: Methodsmentioning

confidence: 99%

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Involvement of human monogenic cardiomyopathy genes in experimental polygenic cardiac hypertrophy

Prestes

Marques

López–Campos

et al. 2018

Physiological Genomics

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Hypertrophic cardiomyopathy thickens heart muscles, reducing functionality and increasing risk of cardiac disease and morbidity. Genetic factors are involved, but their contribution is poorly understood. We used the hypertrophic heart rat (HHR), a unique normotensive polygenic model of cardiac hypertrophy and heart failure, to investigate the role of genes associated with monogenic human cardiomyopathy. We selected 42 genes involved in monogenic human cardiomyopathies to study: 1) DNA variants, by sequencing the whole genome of 13-wk-old HHR and age-matched normal heart rat (NHR), its genetic control strain; 2) mRNA expression, by targeted RNA-sequencing in left ventricles of HHR and NHR at 5 ages (2 days old and 4, 13, 33, and 50 wk old) compared with human idiopathic dilated cardiomyopathy data; and 3) microRNA expression, with rat microRNA microarrays in left ventricles of 2-day-old HHR and age-matched NHR. We also investigated experimentally validated microRNA-mRNA interactions. Whole-genome sequencing revealed unique variants mostly located in noncoding regions of HHR and NHR. We found 29 genes differentially expressed in at least 1 age. Genes encoding desmoglein 2 ( Dsg2) and transthyretin ( Ttr) were significantly differentially expressed at all ages in the HHR, but only Ttr was also differentially expressed in human idiopathic cardiomyopathy. Lastly, only two microRNAs differentially expressed in the HHR were present in our comparison of validated microRNA-mRNA interactions. These two microRNAs interact with five of the genes studied. Our study shows that genes involved in monogenic forms of human cardiomyopathies may also influence polygenic forms of the disease.

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“…DNA sequence variants in HHR were identified according to methods detailed previously (30). Briefly, we sequenced the whole genome of 1 male 13-wk-old NHR and 1 age-matched HHR.…”

Section: Methodsmentioning

confidence: 99%

“…Variants were analyzed according to Genome Analysis Toolkit best practices (35), and functional annotation was performed using SnpEff software (4). Results were stored in a database developed in house, and then we identified unique single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) in the NHR and HHR (30). Fig.…”

Section: Methodsmentioning

confidence: 99%

Involvement of human monogenic cardiomyopathy genes in experimental polygenic cardiac hypertrophy

Prestes

Marques

López–Campos

et al. 2018

Physiological Genomics

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“…Recently, the results of a randomized study indicated that MuRF1 expression decreased in the skeletal muscle of patients with chronic heart failure after they completed exercise training [69]. In a spontaneous cardiac hypertrophy mouse model, Prestes et al [70] found that MuRF2 is a novel candidate gene for cardiac hypertrophy. The functions of MuRF2 and MuRF3 also overlap during binding to microtubules, and both are involved in sarcomere formation.…”

Section: Muscle Ring Finger Protein Familymentioning

confidence: 99%

Emerging Role of TRIM Family Proteins in Cardiovascular Disease

Zhang

et al. 2020

Cardiology

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Ubiquitination is one of the basic mechanisms of cell protein homeostasis and degradation and is accomplished by 3 enzymes, E1, E2, and E3. Tripartite motif-containing proteins (TRIMs) constitute the largest subfamily of RING E3 ligases, with > 70 current members in humans and mice. These members are involved in multiple biological processes, including growth, differentiation, and apoptosis as well as disease and tumorigenesis. Accumulating evidence has shown that many TRIM proteins are associated with various cardiac processes and pathologies, such as heart development, signal transduction, protein degradation, autophagy mediation, ion channel regulation, congenital heart disease, and cardiomyopathies. In this review, we provide an overview of the TRIM family and discuss its involvement in the regulation of cardiac proteostasis and pathophysiology and its potential therapeutic implications.

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“…Tripartite motif-containing protein 44 (Trim44), which was first cloned in 2001 by Effrossini Boutou et al (2001) , has been identified as a member of the TRIM protein family. TRIM family proteins, most of which have E3 ubiquitin ligase activities, are involved in a variety of cellular processes, such as apoptosis, development, growth and signal transduction ( Di Fiore et al, 2003 ; Hershko and Ciechanover, 1998 ; Yang et al, 2020 ; Chen et al, 2016 , 2017 ; Prestes et al, 2016 ; Heliste et al, 2020 ; Zungu et al, 2011 ; Salazar-Mendiguchía et al, 2020 ). TRIM family proteins are also involved in multiple diseases, including those affecting innate immunity and neurodevelopment, cardiovascular diseases and carcinogenesis ( Yang et al, 2013 ; Leong et al, 2002 ; Hatakeyama, 2011 ; Järvinen et al, 2008 ; Urano et al, 2009 ; Boutou et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway

Jiang

Guan

et al. 2022

Disease Models &Amp; Mechanisms

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When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and effective intervention targets. Here, myocardium-specific Trim44 knockout rats were generated using CRISPR-Cas9 technology. Cardiac phenotypic observations revealed that Trim44 knockout affected cardiac morphology at baseline. Rats with Trim44 deficiency exhibited resistance to cardiac pathological changes in response to stimulation via isoproterenol (ISO) treatment, including improvement of cardiac remodeling and dysfunction by morphological and functional observations, reduced myocardial fibrosis and reduced expression of molecular markers of cardiac stress. Furthermore, signal transduction validation associated with growth and hypertrophy development in vivo and in vitro demonstrated that Trim44 deficiency inhibited the activation of signaling pathways involved in myocardial hypertrophy, especially response to pathological stress. In conclusion, the present study indicates that Trim44 knockout attenuates ISO-induced pathological cardiac remodeling through blocking the AKT/mTOR/GSK3β/P70S6K signaling pathway. This is the first study to demonstrate the function and importance of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy and HF.

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Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22

Abstract: Our study suggests that the Trim55 gene, located in Cm22, is a novel candidate gene for polygenic LV hypertrophy independent of blood pressure.

Cited by 7 publications

References 37 publications

Involvement of human monogenic cardiomyopathy genes in experimental polygenic cardiac hypertrophy

Involvement of human monogenic cardiomyopathy genes in experimental polygenic cardiac hypertrophy

Emerging Role of TRIM Family Proteins in Cardiovascular Disease

Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway

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