Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy

Tallo, Christian A; Duncan, Laura; Yamamoto, Akihiko; Slaydon, Joshua D; Arya, Gunjan H.; Turlapati, Lavanya; Mackay, Trudy F. C.; Carbone, Mary Anna

doi:10.1093/g3journal/jkaa014

Cited by 5 publications

(5 citation statements)

References 128 publications

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“…The Drosophila model has helped to identify novel genes and pathways involved in arrhythmias [47], atrial fibrillation [80], and channelopathies [81]. It has also been applied to modeling cardiac aging [51], and cardiomyopathies including dilated [82][83][84][85][86][87], hypertrophic [88][89][90], and restrictive cardiomyopathy [82,91,92], in which heart failure could occur [43]. Finally, the developed Drosophila models of muscular diseases with cardiac symptoms such as DM1 have been instrumental in dissecting the gene deregulations underlying heart defects and in identifying new therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Drosophila Heart as a Model for Cardiac Development and Diseases

Souidi

Jagla

2021

Cells

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The Drosophila heart, also referred to as the dorsal vessel, pumps the insect blood, the hemolymph. The bilateral heart primordia develop from the most dorsally located mesodermal cells, migrate coordinately, and fuse to form the cardiac tube. Though much simpler, the fruit fly heart displays several developmental and functional similarities to the vertebrate heart and, as we discuss here, represents an attractive model system for dissecting mechanisms of cardiac aging and heart failure and identifying genes causing congenital heart diseases. Fast imaging technologies allow for the characterization of heartbeat parameters in the adult fly and there is growing evidence that cardiac dysfunction in human diseases could be reproduced and analyzed in Drosophila, as discussed here for heart defects associated with the myotonic dystrophy type 1. Overall, the power of genetics and unsuspected conservation of genes and pathways puts Drosophila at the heart of fundamental and applied cardiac research.

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Section: Discussionmentioning

confidence: 99%

Drosophila Heart as a Model for Cardiac Development and Diseases

Souidi

Jagla

2021

Cells

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“…34 When the A31P mutation is transferred into fruit flies (Drosophila melanogaster), numerous abnormalities are produced including downregulation of small nucleolar RNAs (a class of small RNA molecules that primarily guide chemical modifications of other RNAs) and the unfolded protein response. 35 Maine Coon cats heterozygous for this mutation develop subtle systolic and diastolic dysfunction but usually do not develop wall thickening and so are subclinical. 36,37 Those that are homozygous for the mutation commonly develop various degrees of wall thickening (HCM), some severe enough to result in severe LA enlargement and hence left heart failure or ATE.…”

Section: Etiologymentioning

confidence: 99%

Section: Etiologymentioning

confidence: 99%

The Feline Cardiomyopathies: 2. Hypertrophic cardiomyopathy

Kittleson

Côté

2021

Journal of Feline Medicine and Surgery

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Practical relevance: Hypertrophic cardiomyopathy (HCM) is the most common form of feline cardiomyopathy observed clinically and may affect up to approximately 15% of the domestic cat population, primarily as a subclinical disease. Fortunately, severe HCM, leading to heart failure or arterial thromboembolism (ATE), only occurs in a small proportion of these cats. Patient group: Domestic cats of any age from 3 months upward, of either sex and of any breed, can be affected. A higher prevalence in male and domestic shorthair cats has been reported. Diagnostics: Subclinical feline HCM may or may not produce a heart murmur or gallop sound. Substantial left atrial enlargement can often be identified radiographically in cats with severe HCM. Biomarkers should not be relied on solely to diagnose the disease. While severe feline HCM can usually be diagnosed via echocardiography alone, feline HCM with mild to moderate left ventricular (LV) wall thickening is a diagnosis of exclusion, which means there is no definitive test for HCM in these cats and so other disorders that can cause mild to moderate LV wall thickening (eg, hyperthyroidism, systemic hypertension, acromegaly, dehydration) need to be ruled out. Key findings: While a genetic cause of HCM has been identified in two breeds and is suspected in another, for most cats the cause is unknown. Systolic anterior motion of the mitral valve (SAM) is the most common cause of dynamic left ventricular outflow tract obstruction (DLVOTO) and, in turn, the most common cause of a heart murmur with feline HCM. While severe DLVOTO is probably clinically significant and so should be treated, lesser degrees probably are not. Furthermore, since SAM can likely be induced in most cats with HCM, the distinction between HCM without obstruction and HCM with obstruction (HOCM) is of limited importance in cats. Diastolic dysfunction, and its consequences of abnormally increased atrial pressure leading to signs of heart failure, and sluggish atrial blood flow leading to ATE, is the primary abnormality that causes clinical signs and death in affected cats. Treatment (eg, loop diuretics) is aimed at controlling heart failure. Preventive treatment (eg, antithrombotic drugs) is aimed at reducing the risk of complications (eg, ATE). Conclusions: Most cats with HCM show no overt clinical signs and live a normal or near-normal life despite this disease. However, a substantial minority of cats develop overt clinical signs referable to heart failure or ATE that require treatment. For most cats with clinical signs caused by HCM, the long-term prognosis is poor to grave despite therapy. Areas of uncertainty: Genetic mutations (variants) that cause HCM have been identified in a few breeds, but, despite valiant efforts, the cause of HCM in the vast majority of cats remains unknown. No treatment currently exists that reverses or even slows the cardiomyopathic process in HCM, again despite valiant efforts. The search goes on.

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“…These snoRNAs may play an important role in post-translational modifications and alternative splicing and may be used as HCM biomarkers or RNA-targeting therapies in the future. Furthermore, Tallo et al made a Drosophila model of feline HCM and conducted transcriptome analyses using RNA-seq ( Tallo et al, 2021 ). They found that snoRNAs were significantly dysregulated in exercised female flies harbouring mutant alleles as opposed to flies that harboured the WT allele.…”

Section: Role Of Snornas In Cvdmentioning

confidence: 99%

Small but strong: the emerging role of small nucleolar RNA in cardiovascular diseases

Sun,

Wang,

Luo

et al. 2023

Front. Cell Dev. Biol.

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Cardiovascular diseases (CVDs) are the leading cause of mortality and disability worldwide. Numerous studies have demonstrated that non-coding RNAs (ncRNAs) play a primary role in CVD development. Therefore, studies on the mechanisms of ncRNAs are essential for further efforts to prevent and treat CVDs. Small nucleolar RNAs (snoRNAs) are a novel species of non-conventional ncRNAs that guide post-transcriptional modifications and the subsequent maturation of small nuclear RNA and ribosomal RNA. Evidently, snoRNAs are extensively expressed in human tissues and may regulate different illnesses. Particularly, as the next-generation sequencing techniques have progressed, snoRNAs have been shown to be differentially expressed in CVDs, suggesting that they may play a role in the occurrence and progression of cardiac illnesses. However, the molecular processes and signaling pathways underlying the function of snoRNAs remain unidentified. Therefore, it is of great value to comprehensively investigate the association between snoRNAs and CVDs. The aim of this review was to collate existing literature on the biogenesis, characteristics, and potential regulatory mechanisms of snoRNAs. In particular, we present a scientific update on these snoRNAs and their relevance to CVDs in an effort to cast new light on the functions of snoRNAs in the clinical diagnosis of CVDs.

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Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy

Cited by 5 publications

References 128 publications

Drosophila Heart as a Model for Cardiac Development and Diseases

Drosophila Heart as a Model for Cardiac Development and Diseases

The Feline Cardiomyopathies: 2. Hypertrophic cardiomyopathy

Small but strong: the emerging role of small nucleolar RNA in cardiovascular diseases

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