GSE112319 Enhancing Cardiac Cell Proliferation and Survival Suppresses Dilated Cardiomyopathy caused by Ttn-insufficiency

Contributors : Jiang Jianming ; Liao DanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusDilated cardiomyopathy (DCM), defined by left ventricular (LV) enlargement associated with impaired cardiac performance, is a major cause of heart failure (HF). This results in a dilated, thin-walled left ventricle that fails to supply sufficient blood to the body. Truncating variants in TTN (TTNtv), coding for the largest structural protein in the sarcomere, contribute to the largest portion of familial and ambulatory DCM. The mechanisms for how TTNtv lead to cardiac dilation are unclear. Here, we show that reduction of Ttn expression by shRNA (Ttn shRNA) generated DCM in both mouse and rat. Ttn shRNA transduced mice developed typical DCM manifestations including impaired cardiac performance, enlarged LV and reduced LV wall thickness. Gene profiling indicates cardiac metabolism, cell proliferation and survival related genes are significantly dysregulated in Ttn shRNA-induced DCM. TUNEL assay showed Ttn shRNA induced a significant increase of cardiac cell apoptosis. A screen of 15 dysregulated downstream genes identified candidates, including Esrra, Esrrb and Yy1 significantly suppressed Ttn shRNA-induced cardiac dilation and/or DCM. Ttn shRNA induced cardiac cell apoptosis was ameliorated by Yy1. Importantly, by inducing D-type cyclin, Yy1 initiated cardiomyocyte cell cycle reentry facilitating the restoration of cardiac performance. Our findings dem...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

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Duchenne muscular dystrophy (DMD) is a devastating and fatal disease affecting ~1 in 3500 boys with dystrophin gene mutations [1,2]. Dystrophin plays important roles in sarcolemma stability and cell signaling in skeletal, smooth, and cardiac muscles [1,2]. DMD patients often die at a young age from dilated cardiomyopathy (DCM) or respiratory dysfunction. The use of ventilators has reduced respiratory failure in DMD patients and DCM associated heart failure (HF) is now a major cause of DMD patient death [1,2].
Source: International Journal of Cardiology - Category: Cardiology Authors: Source Type: research
Abstract The more common manifestations of cryptococcal infections are restricted to the central nervous system and lungs. A young man, suffering from idiopathic dilated cardiomyopathy with a left ventricular ejection fraction of 20%, presented with subacute, painful tender swelling in both legs initially attributed to congestive cardiac failure. No response to diuretics was achieved. Metabolically active lesions in the muscles of both lower limbs suggestive of muscle abscesses were found. A diagnosis of tropical pyomyositis was therefore made, but aspiration surprisingly revealed gram-positive yeast cells, staini...
Source: Tropical Doctor - Category: Tropical Medicine Authors: Tags: Trop Doct Source Type: research
AbstractThe use of cocaine constitutes a major health problem. Cocaine use is associated with acute and chronic complications that might involve any system, the most common being the cardiovascular system. The precise incidence of cocaine-induced cardiomyopathy remains mysterious and probably underreported. Cocaine use should be considered in young patients presenting with chest pain or heart failure without other underlying risk factors. Cocaine-related cardiovascular complications can be acute or chronic and include ischemic and non-ischemic events. Frequent cocaine users have a seven-fold higher risk of myocardial infar...
Source: Heart Failure Reviews - Category: Cardiology Source Type: research
Authors: Liu Y, Jiang B, Cao Y, Chen W, Yin L, Xu Y, Qiu Z Abstract Dilated cardiomyopathy (DCM) is a disease that can lead to heart expansion and severe heart failure, but the specific pathogenesis remains unclear. Sox5 is a member of the Sox family with a key role in cardiac function. However, the role of Sox5 in DCM remains unclear. In the present study, wild‑type mice were intraperitoneally injected with doxorubicin (Dox) to induce DCM, and heart specimens from human patients with DCM were used to investigate the preliminary role of Sox5 in DCM. The present study demonstrated that, compared with control human...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
AbstractAimsThe alarmin S100A8/S100A9 (S100A8/A9) is released by activated monocytes/macrophages and neutrophils in the setting lymphocytic myocarditis (MC). We recently demonstrated its therapeutic potential in experimental acute MC. Now, we investigated the diagnostic relevance of S100A8/A9 serum levels in patients with suspected acute and chronic MC and in patients with heart failure without cardiac inflammation.Methods and ResultsSerum S100A8/A9 levels were analysed in patients with a recent onset of MC [ ≤ 30 days,n = 32; ejection fraction (EF): 45.4 ± 12.9%], dilated cardiomyopathy ...
Source: ESC Heart Failure - Category: Cardiology Authors: Tags: Original Research Article Source Type: research
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Source: Circulation Journal - Category: Cardiology Authors: Tags: Circ J Source Type: research
Authors: Samejima Y, Iuchi A, Kanai T, Noda Y, Nasu S, Tanaka A, Morishita N, Suzuki H, Okamoto N, Harada H, Ezumi A, Ueda K, Kawahara K, Hirashima T Abstract Cardiac side effects associated with immune checkpoint inhibitors (ICIs) are an uncommon but serious complication with a relatively high mortality. We experienced a case of cardiomyopathy induced by nivolumab. Echocardiography showed diffuse hypo-kinesis of the left ventricular cardiac wall and a significant decrease in the ejection fraction, like dilated cardiomyopathy. The myocardial biopsy showed non-inflammatory change; cardiac function gradually improved...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Source: Journal of Nuclear Cardiology - Category: Nuclear Medicine Source Type: research
AbstractBackgroundContemporary survival trends of Dilated Cardiomyopathy (DCM) patients are largely unknown. The aims of this study are to describe clinical descriptors, survival trends and the prognostic impact of etiological characterization in DCM patients.MethodsDCM patients were consecutively enrolled and divided into 4 groups according to the period of enrolment: 1st: 1978 ‐1984; 2nd: 1985 ‐1994; 3rd: 1995 ‐2004; 4th: 2005 ‐2015. A cohort of patients with DCM with specific etiology, enrolled from 2005 to 2015, was also analyzed.ResultsOver a mean follow ‐up of 12±8 years, 1284 DCM patients (52...
Source: European Journal of Heart Failure - Category: Cardiology Authors: Tags: Research Article Source Type: research
ConclusionsThe conformational auto ‐epitope targeted by cardio‐pathogenic β1‐receptor autoantibodies is faithfully conserved in cyclopeptide homologues of the β1ECII loop bearing the NDPK211 –214 motif and the C209↔C215 bridge while lacking cysteine C216. Such molecules provide promising tools for novel diagnostic and therapeutic approaches in β1‐autoantibody‐positive CHF.
Source: ESC Heart Failure - Category: Cardiology Authors: Tags: Original Research Article Source Type: research
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