Glycogen storage in a zebrafish Pompe disease model is reduced by 3-BrPA treatment
Publication date: Available online 7 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Cinzia Bragato, Silvia Carra, Flavia Blasevich, Franco Salerno, Alessia Brix, Andrea Bassi, Monica Beltrame, Franco Cotelli, Lorenzo Maggi, Renato Mantegazza, Marina MoraAbstractPompe disease (PD) is an autosomal recessive muscular disorder caused by deficiency of the glycogen hydrolytic enzyme acid α-glucosidase (GAA). The enzyme replacement therapy, currently the only available therapy for PD patients, is efficacious in improving cardiomyopathy in the infantile form, but not equally effective in the late onset cases with involvement of skeletal muscle. Correction of the skeletal muscle phenotype has indeed been challenging, probably due to concomitant dysfunctional autophagy. The increasing attention to the pathogenic mechanisms of PD and the search of new therapeutic strategies prompted us to generate and characterize a novel transient PD model, using zebrafish. Our model presented increased glycogen content, markedly altered motor behavior and increased lysosome content, in addition to altered expression of the autophagy-related transcripts and proteins Beclin1, p62 and Lc3b. Furthermore, the model was used to assess the beneficial effects of 3-bromopyruvic acid (3-BrPA). Treatment with 3-BrPA induced amelioration of the model phenotypes regarding glycogen storage, motility behavior and autophagy-related transcripts and proteins. Our ze...
Left ventricular noncompaction cardiomyopathy is a heart disease with relevant potential complications including heart failure, life-threatening arrhythmias, and embolic events. In order to prevent adverse outcomes, it is crucial to appropriately recognize and manage this cardiomyopathy. In this paper, we report the main clinical presentations and imaging modalities used for diagnosis, including echocardiography and magnetic resonance imaging. We highlight the role of a comprehensive functional cardiac evaluation and the possible prognostic implications of both systolic and diastolic dysfunction. Furthermore, we summarize ...
This article will provide a comprehensive review and update on this important disease state.
Transthyretin (TTR) amyloid cardiomyopathy is a life-threatening condition in which amyloid fibrils accumulate in the heart, eventually leading to cardiac symptomatology and death. To date, treatment of this condition has been directed at symptom relief due to a lack of effective treatment options which target the cause of the disease. The discovery that amyloid deposition was a result of dissociation of the TTR protein structure allowed for the development of tafamidis, which acts by stabilizing the TTR tetramer. Due to the rare nature of the disease, there is limited clinical trial data with tafamidis, with the largest c...
Publication date: July 2020Source: Biomedicine &Pharmacotherapy, Volume 127Author(s): Zhongyuan Wang, Yunfeng Zhu, Yanhua Zhang, Jie Zhang, Tianjiao Ji, Weizu Li, Weiping Li
Condition: Hypertrophic Obstructive Cardiomyopathy Intervention: Other: The Septal myectom Sponsor: Assiut University Not yet recruiting
Publication date: Available online 30 March 2020Source: Redox BiologyAuthor(s): Cheng Zeng, Fengqi Duan, Jia Hu, Bin Luo, Binlong Huang, Xiaoying Lou, Xiuting Sun, Hongyu Li, Xuanhong Zhang, Shengli Yin, Hongmei Tan
Amyloid transthyretin (ATTR) cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy and associated heart failure with preserved ejection fraction (HFpEF). Despite improved diagnostic techniques to identify this condition, many patients experience delayed diagnosis. Interpretation of routine cardiac biomarkers (i.e. troponins and brain natriuretic peptide (BNP)) and echocardiography in ATTR-CA is limited, particularly in relation to pyrophosphate (PYP) scintigraphy.
Guideline directed medical therapy with beta blockers, ACEi/ARBs, and aldosterone antagonists with the goal of affecting cardiac reverse remodeling (CRR) has previously been the cornerstone of management of patients with heart failure with reduced ejection fraction (HFrEF). More recently, PARADIGM-HF demonstrated the superiority of sacubitril-valsartan to enalapril in reducing HF hospitalizations as well as cardiac and all-cause mortality. Other studies demonstrated that ARNI therapy may enhance CRR to a greater degree than ACEI or ARB therapy alone.
Functional mitral regurgitation (FMR) in non-ischemic cardiomyopathy (NICM) may be partly related to the dysfunction of subvalvular apparatus. Thus, we sought to investigate the correlation between papillary muscle viability and FMR changes in NICM.
Patients with dilated cardiomyopathy (DCM) who achieved left ventricular reverse remodeling (LVRR) have a favorable prognosis, but it is still difficult to precisely predict LVRR in the clinical setting.