Various Types Of Cardiomyopathy Research Articles

Krüpple-like factors in cardiomyopathy: emerging player and therapeutic opportunities.

Cardiomyopathy, a heterogeneous pathological condition characterized by changes in cardiac structure or function, represents a significant risk factor for the prevalence and mortality of cardiovascular disease (CVD). Research conducted over the years has led to the modification of definition and classification of cardiomyopathy. Herein, we reviewed seven of the most common types of cardiomyopathies, including Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), diabetic cardiomyopathy, Dilated Cardiomyopathy (DCM), desmin-associated cardiomyopathy, Hypertrophic Cardiomyopathy (HCM), Ischemic Cardiomyopathy (ICM), and obesity cardiomyopathy, focusing on their definitions, epidemiology, and influencing factors. Cardiomyopathies manifest in various ways ranging from microscopic alterations in cardiomyocytes, to tissue hypoperfusion, cardiac failure, and arrhythmias caused by electrical conduction abnormalities. As pleiotropic Transcription Factors (TFs), the Krüppel-Like Factors (KLFs), a family of zinc finger proteins, are involved in regulating the setting and development of cardiomyopathies, and play critical roles in associated biological processes, including Oxidative Stress (OS), inflammatory reactions, myocardial hypertrophy and fibrosis, and cellular autophagy and apoptosis, particularly in diabetic cardiomyopathy. However, research into KLFs in cardiomyopathy is still in its early stages, and the pathophysiologic mechanisms of some KLF members in various types of cardiomyopathies remain unclear. This article reviews the roles and recent research advances in KLFs, specifically those targeting and regulating several cardiomyopathy-associated processes.

Fragmented QRS, a strong predictor of mortality and major arrhythmic events in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all-cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta-analysis study. We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case-control, or analytical cross-sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all-cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using "Comprehensive Meta-Analysis" software, Version 2.0. Nineteen cohort and three analytical cross-sectional studies were included in this meta-analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all-cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388-2.656, p < 0.0001/pooled HR: 1.729; 95% CI: 1.327-2.251, p < 0.0001). Also, the risk of developing MAEs in the presence of fQRS was significantly increased (pooled RR: 2.041; 95% CI: 1.644-2.533, p < 0.0001/pooled HR: 3.626; 95% CI: 2.119-6.204, p < 0.0001). In the subgroup analysis, the strongest association between fQRS presence and increased MAEs was observed in patients with hypertrophic cardiomyopathy (HCM) (pooled RR: 3.44; 95% CI: 2.07-5.71, p < 0.0001/pooled HR: 3.21; 95% CI: 2.04-5.06, p < 0.0001). Fragmented QRS could be a prognostic marker for all-cause mortality and MAEs in patients with various types of nonischemic cardiomyopathies, particularly HCM.

Differences in Androgen Receptor Expression in Human Heart Tissue in Various Types of Cardiomyopathy and in Aortic Valve Stenosis.

Background: Sex-specific differences in heart disease outcomes are influenced by the levels of the steroid hormones, estrogen and testosterone. While the roles of estrogen receptors in cardiac disease are well-studied in animals and humans, respective research on androgen receptors (AR) is limited. Here we investigate AR protein and mRNA expression in human myocardium of various cardiac diseases. Methods: AR expression was analyzed by western blotting in myocardium from human non-failing hearts (NF, n = 6) and patients with aortic stenosis (AS, n = 6), hypertrophic cardiomyopathy (HCM, n = 7), dilated cardiomyopathy (DCM, n = 7), and ischemic cardiomyopathy (ICM, n = 7). Using an AR45-specific antibody, a subsequent western blot assessed samples from male and female patients with HCM (n = 10) and DCM (n = 10). The same sample set was probed for full-length AR and AR45 mRNA expression. Immunohistochemistry (IHC) localized AR in myocardium from HCM and AS hearts. Results: Full-length AR was notably enriched in AS and HCM hearts compared to ICM, DCM, and NF. Similarly, AR45 was more abundant in HCM than in DCM. In contrast to the pattern observed for AR protein, full-length AR mRNA levels were lower in HCM compared to DCM, with no discernible difference for the AR45 isoform. Although gender differences in AR expression were not detected in western blots or qRT-PCR, IHC showed stronger nuclear AR signals in males than in females. Conclusions: Our findings indicate disease-specific regulation of AR mRNA and/or AR protein in cardiac hypertrophy, underscoring a potential role in this cardiac pathology.

The role of noncoding genetic variants in cardiomyopathy.

Cardiomyopathies remain one of the leading causes of morbidity and mortality worldwide. Environmental risk factors and genetic predisposition account for most cardiomyopathy cases. As with all complex diseases, there are significant challenges in the interpretation of the molecular mechanisms underlying cardiomyopathy-associated genetic variants. Given the technical improvements and reduced costs of DNA sequence technologies, an increasing number of patients are now undergoing genetic testing, resulting in a continuously expanding list of novel mutations. However, many patients carry noncoding genetic variants, and although emerging evidence supports their contribution to cardiac disease, their role in cardiomyopathies remains largely understudied. In this review, we summarize published studies reporting on the association of different types of noncoding variants with various types of cardiomyopathies. We focus on variants within transcriptional enhancers, promoters, intronic sites, and untranslated regions that are likely associated with cardiac disease. Given the broad nature of this topic, we provide an overview of studies that are relatively recent and have sufficient evidence to support a significant degree of causality. We believe that more research with additional validation of noncoding genetic variants will provide further mechanistic insights on the development of cardiac disease, and noncoding variants will be increasingly incorporated in future genetic screening tests.

Cryptotanshinone Attenuated Pathological Cardiac Remodeling In Vivo and In Vitro Experiments.

Cardiac remodeling has been demonstrated to be the early stage and common pathway for various types of cardiomyopathy, but no specific treatment has been suggested to prevent its development and progress. This study was aimed at assessing whether Cryptotanshinone (CTS) treatment could effectively attenuate cardiac remodeling in vivo and in vitro. Aortic banding (AB) surgery was performed to establish a pressure-overload-induced mouse cardiac remodeling model. Echocardiography and pressure-volume proof were used to examine mouse cardiac function. Hematoxylin and eosin (HE) and Picro-Sirius Red (PSR) staining were used to assess cardiac remodeling in vivo. Mouse hearts were collected to analysis signaling pathway and cardiac remodeling markers, respectively. Furthermore, neonatal rat cardiomyocyte (NRCMs) and cardiac fibroblast (CF) were isolated to investigate the roles and mechanisms of CTS treatment in vitro. CTS administration significantly alleviated pressure-overload-induced mouse cardiac dysfunction, inhibited cardiac hypertrophy, and reduced cardiac fibrosis. Mechanically, CTS treatment significantly inhibited the STAT3 and TGF-β/SMAD3 signaling pathways. In vitro experiments, CTS treatment markedly inhibited AngII-induced cardiomyocyte hypertrophy and TGF-β-induced myofibroblast activation via inhibiting STAT3 phosphorylation and its nuclear translocation. Finally, CTS treatment could not protect against pressure overload-induced mouse cardiac remodeling after adenovirus-associated virus (AAV)9-mediated STAT3 overexpression in mouse heart. CTS treatment might attenuate pathological cardiac remodeling via inhibiting STAT3-dependent pathway.

Generation of three TTN knock-out human induced pluripotent stem cell lines using CRISPR/Cas9 system

TTN mutations are the common genetic cause for various types of cardiomyopathies (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy) and skeletal myopathies. Here, we generated three TTN knock-out human induced pluripotent stem cell (iPSC) lines using CRISPR/Cas9 system. These cell lines, which exhibit normal karyotype, typical morphology and pluripotency, could provide useful platform for investigating the role of TTN in associated disorders.

Abstract 10850: Investigating the Role of a Cardiac Enhancer in the Development of Heart Failure

Introduction: Alpha actinin-2 (ACTN2) is a major cytoskeletal protein that plays a critical role in maintaining the structural and functional integrity of the sarcomere. ACTN2 mutations, although rare, have been shown to be associated with various types of cardiomyopathy. Using genome-wide association and multi-omic approaches, we recently identified non-coding variants that showed a strong association with heart failure (HF). Two of the variants are within an evolutionary conserved transcriptional enhancer region that regulates the ACTN2 gene in human stem cell derived cardiomyocytes (hPSC-CMs). However, the role of cardiac enhancers in the development of HF remains unknown, therefore we used engineered heart tissues (EHT) from hPSC-CMs to investigate the effects of the ACTN2 enhancer. Methods: We used hPSC-CMs and performed morphologic and functional analyses by immunostaining, calcium transient measurements and quantitative assays such as western blotting, proteomics, qPCR and single cell transcriptomics. Next, we utilized CRISPR interference (CRISPRi) and chromatin immunoprecipitation (ChIP) to analyze the transcriptional regulation of the ACTN2 enhancer. Finally, we measured force generation using EHTs. Results: We first engineered hPSC-CMs carrying an ACTN2 enhancer deletion. This resulted in decreased ACTN2 gene and protein expression, and cardiomyocytes developed myofibrillar disarray, hypertrophy, lower beating rates and suppressed calcium transients. Moreover, EHTs demonstrated reduced mechanical force. Using CRISPRi and ChIP we found that the transcription factor MEF2c binds a short DNA sequence containing an enhancer variant to regulate ACTN2 expression. Single cell RNA-Seq analysis of hPSC-CMs treated with isoproterenol to model the hyperadrenergic state observed in HF, revealed the induction of pathways involved in protein quality control, actin fragmentation and apoptosis. We have also recently developed a mouse model to address the effect of the enhancer in vivo . Conclusions: Our study confirms that a conserved and clinically relevant enhancer region can effectively regulate ACTN2 , and variants within that region can have detrimental consequences on CMs which can contribute to HF.

Classification of Cardiomyopathies from MR Cine Images Using Convolutional Neural Network with Transfer Learning.

The automatic classification of various types of cardiomyopathies is desirable but has never been performed using a convolutional neural network (CNN). The purpose of this study was to evaluate currently available CNN models to classify cine magnetic resonance (cine-MR) images of cardiomyopathies. Method: Diastolic and systolic frames of 1200 cine-MR sequences of three categories of subjects (395 normal, 411 hypertrophic cardiomyopathy, and 394 dilated cardiomyopathy) were selected, preprocessed, and labeled. Pretrained, fine-tuned deep learning models (VGG) were used for image classification (sixfold cross-validation and double split testing with hold-out data). The heat activation map algorithm (Grad-CAM) was applied to reveal salient pixel areas leading to the classification. Results: The diastolic–systolic dual-input concatenated VGG model cross-validation accuracy was 0.982 ± 0.009. Summed confusion matrices showed that, for the 1200 inputs, the VGG model led to 22 errors. The classification of a 227-input validation group, carried out by an experienced radiologist and cardiologist, led to a similar number of discrepancies. The image preparation process led to 5% accuracy improvement as compared to nonprepared images. Grad-CAM heat activation maps showed that most misclassifications occurred when extracardiac location caught the attention of the network. Conclusions: CNN networks are very well suited and are 98% accurate for the classification of cardiomyopathies, regardless of the imaging plane, when both diastolic and systolic frames are incorporated. Misclassification is in the same range as inter-observer discrepancies in experienced human readers.

B-AB08-01 SUDDEN CARDIAC DEATH IN THE YOUNG IN THE UNITED STATES FROM 2015 TO 2018

Sudden cardiac death in the young (SCDY) is incompletely described. The NIH/CDC Sudden Death in the Young (SDY) Case Registry collects standardized, population-based data. To explore mortality rates and characteristics of SCDY. Using SDY Case Registry data, we analyzed sudden, unexpected deaths from 2015-2018 categorized as Explained Cardiac (EC) (definitive cardiac cause identified after investigation) among residents 0-17 years old in 9 states/jurisdictions. We described demographics, diagnoses, and activity level, and calculated population-based mortality rates. Among 2,153 Registry cases, 95 were categorized as EC (29 infants [<1 year], 66 children). Most cases were autopsied (98%). The EC mortality rate was 0.37/100,000 child population. (Table) EC was more frequent among infants and children 1 or 14-17 years than children 2-13 years. EC was more common among males and black children. The most common causes of EC were myocarditis, congenital heart disease (CHD), and hypertrophic cardiomyopathy (HCM). In infants, CHD and myocarditis predominated. Among 14-17 year-old children, the most common causes of EC were HCM and coronary anomalies. More EC cases occurred at rest. Most exertional deaths occurred in 14-17 year-old children and were due to coronary artery anomalies, myocarditis, and various types of cardiomyopathy. Of the deaths during rest, myocarditis the was most common cause. The SDY Case Registry provides important information on SCDY in the US population. Exploring age differences in EC causes may inform prevention efforts.

Role of Cardiac MRI in Assessment Non-Ischemic Cardiomyopathy

Background: cardiomyopathies include a broad spectrum of myocardial problems which can affect the heart either a primary disease process or as part of a systemic disorder, which may be complicated by heart failure or death. Objective: the aim of the study to identify the role of cardiac magnetic resonance imaging to diagnose the different various types of cardiomyopathy. Patients and Methods: this study included 50 patients with suspected different types of non-ischemic cardiomyopathies referred from outpatient clinic of Cardiology at Al-Hussein University hospital from November 2018 to July 2019. Results: all patients showed mild to moderate mitral regurge (100% of cases), tricuspid regurge was seen in 3 cases (75% of cases) and aortic regurge was seen in 4 cases (50% of cases). The most value of MRI study of these patients was to differentiate whether if heart failure is related to 1ry dilated cardiomyopathy or other causes such as ischemia as they have different management in each group. Conclusion: CMR is a valuable (minimally or non-invasive) imaging technique in patients with suspected or known to have non-ischemic cardiomyopathies. It helps to identify the underlying cause, prognosis and responsiveness to therapy and affect management as well follow-up and most recently as a preventive diagnostic tool.

The Role of Matrix Metalloproteinases in the Progression and Vulnerabilization of Coronary Atherosclerotic Plaques

Abstract Extracellular matrix (ECM) plays an important role in the development and progression of atherosclerotic lesions. Changes in the ECM are involved in the pathophysiology of many cardiovascular diseases, including atherosclerosis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases, also known as matrixins, with proteolytic activity in the ECM, being responsible for the process of tissue remodeling in various systemic pathologies, including cardiac and vascular diseases. MMPs play an important role in maintaining normal vascular structure, but also in secondary cardiovascular remodeling, in the formation of atherosclerotic plaques and in their vulnerabilization process. In addition to the assigned effect of MMPs in vulnerable plaques, they have a well-defined role in post-infarction ventricular remodeling and in various types of cardiomyopathies, followed by onset of congestive heart failure, with repeated hospitalizations and death. The aim of this manuscript was to provide a summary on the role of serum matrix metalloproteinases in the process of initiation, progression and complication of atherosclerotic lesions, from a molecular level to clinical applicability and risk prediction in patients with vulnerable coronary plaques.

Functional characterization of novel alpha-helical rod domain desmin (DES) pathogenic variants associated with dilated cardiomyopathy, atrioventricular block and a risk for sudden cardiac death

BackgroundDesmin is the major intermediate filament (IF) protein in human heart and skeletal muscle. So-called ‘desminopathies’ are disorders due to pathogenic variants in the DES gene and are associated with skeletal myopathies and/or various types of cardiomyopathies. So far, only a limited number of DES pathogenic variants have been identified and functionally characterized. Methods and resultsUsing a Sanger- and next generation sequencing (NGS) approach in patients with various types of cardiomyopathies, we identified two novel, non-synonymous missense DES variants: p.(Ile402Thr) and p.(Glu410Lys). Mutation carriers developed dilated (DCM) or arrhythmogenic cardiomyopathy (ACM), and cardiac conduction disease, leading to spare out the exercise-induced polymorphic ventricular tachycardia; we moved this variant to data in brief. To investigate the functional impact of these four DES variants, transfection experiments using SW-13 and H9c2 cells with native and mutant desmin were performed and filament assembly was analyzed by confocal microscopy. The DES_p.(Ile402Thr) and DES_p.(Glu410Lys) cells showed filament assembly defects forming cytoplasmic desmin aggregates. Furthermore, immunohistochemical and ultrastructural analysis of myocardial tissue from mutation carriers with the DES_p.(Glu410Lys) pathogenic variant supported the in vitro results. ConclusionsOur in vitro results supported the classification of DES_p.(Ile402Thr) and DES_p.(Glu410Lys) as novel pathogenic variants and demonstrated that the cardiac phenotypes associated with DES variants are diverse and cell culture experiments improve in silico analysis and genetic counseling because the pathogenicity of a variant can be clarified.

Cardiomyopathies: echocardiographic profiles based on principal component factor analysis in men and women

Aim. To determine echocardiographic profiles and their prognostic value using factor analysis in men and women with various types of cardiomyopathies (CMP).Material and methods. The study involved 100 people with CMP — 69 men with a median age of 53 years and 31 women with a median age of 58 years. Among the subjects, six nosological types corresponding to ICD 10 classification were revealed: dilated CMP (DCM), ischemic CMP (ICM), alcoholic CMP, mixed CMP, hypertrophic CMP (HCM) and myocarditis. All persons underwent an echocardiography. Echocardiography results as variables were included in factor analysis. The resulting two factors are presented as the first and second echocardiographic profiles.Results. The first echocardiographic profile was characterized as the degree of myocardial contractile function reduction. A strong association of the first profile with DCM, alcoholic CMP and myocarditis in men (p=0,001) and DCM in women (p=0,05) was obtained. In some individuals with ICM and mixed CMP, there was no association with the first profile. The second echocardiographic profile reflected the degree of myocardial mass increase and had significant differences only in women (p=0,04). A strong correlation with the second profile was observed in HCM, in the majority of women with ICM and in some persons with mixed CMP. Fatal outcomes in men were recorded in patients with ICM (66,7%), alcoholic CMP and myocarditis, and in women with mixed CMP (11,1%).Conclusion. For patients with DCM, myocarditis, and alcoholic CMP, the first echocardiographic profile with a risk of death is characteristic. The second echocardiographic profile was inherent in HCM and was associated with a protective effect in women with ICM. The revealed echocardiographic profiles can be extrapolated to nosological types of CMP in men and women in order to verify the diagnosis and prognosis.

Modeling Inherited Cardiomyopathies in Adult Zebrafish for Precision Medicine.

Cardiomyopathies are a highly heterogeneous group of heart muscle disorders. More than 100 causative genes have been linked to various cardiomyopathies, which explain about half of familial cardiomyopathy cases. More than a dozen candidate therapeutic signaling pathways have been identified; however, precision medicine is not being used to treat the various types of cardiomyopathy because knowledge is lacking for how to tailor treatment plans for different genetic causes. Adult zebrafish (Danio rerio) have a higher throughout than rodents and are an emerging vertebrate model for studying cardiomyopathy. Herein, we review progress in the past decade that has proven the feasibility of this simple vertebrate for modeling inherited cardiomyopathies of distinct etiology, identifying effective therapeutic strategies for a particular type of cardiomyopathy, and discovering new cardiomyopathy genes or new therapeutic strategies via a forward genetic approach. On the basis of this progress, we discuss future research that would benefit from integrating this emerging model, including discovery of remaining causative genes and development of genotype-based therapies. Studies using this efficient vertebrate model are anticipated to significantly accelerate the implementation of precision medicine for inherited cardiomyopathies.

Mutations of mtDNA in some Vascular and Metabolic Diseases

The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and, as a result, death. In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases, such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies, and type 2 diabetes mellitus. The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis. The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension, and various types of cardiomyopathies. The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for the treatment of these pathologies. MtDNA mutations associated with the absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of the said diseases.

Основные аспекты биохимии, физиологии сердечных тропонинов

Cardiac troponins (troponin I, T, and C) play an important role in the regulation of contractile function of the heart muscle. Mutations in cardiac troponins are associated with the development of various types of cardiomyopathies, which lead to heart failure and death. The determination of the concentration of cardiac troponins in the blood is used in the diagnosis of some cardiovascular diseases, including acute myocardial infarction, myocarditis, heart failure. This review summarizes the available data on the structure and functions of cardiac troponins, their role in the regulation of myocardial contractions and clinical application.

Thin filament dysfunctions caused by mutations in tropomyosin Tpm3.12 and Tpm1.1

Tropomyosin is the major regulator of the thin filament. In striated muscle its function is to bind troponin complex and control the access of myosin heads to actin in a Ca2+-dependent manner. It also participates in the maintenance of thin filament length by regulation of tropomodulin and leiomodin, the pointed end-binding proteins. Because the size of the overlap between actin and myosin filaments affects the number of myosin heads which interact with actin, the filament length is one of the determinants of force development. Numerous point mutations in genes encoding tropomyosin lead to single amino acid substitutions along the entire length of the coiled coil that are associated with various types of cardiomyopathy and skeletal muscle disease. Specific regions of tropomyosin interact with different binding partners; therefore, the mutations affect diverse tropomyosin functions. In this review, results of studies on mutations in the genes TPM1 and TPM3, encoding Tpm1.1 and Tpm3.12, are described. The paper is particularly focused on mutation-dependent alterations in the mechanisms of actin-myosin interactions and dynamics of the thin filament at the pointed end.

Role of Cardiac MRI in assessment Non-Ischemic Cardiomyopathy

Background: cardiomyopathies encompass a broad spectrum of myocardial conditions which can affect the heart as a primary disease process or as part of a systemic disorder, evolving toward heart failure or cardiovascular death. Objective: this study aimed to identify the role and diagnostic potential of cardiac magnetic resonance imaging to diagnose and differentiate various types of cardiomyopathy. Patients and Methods: this study included 50 patients with suspected different types of non-ischemic cardiomyopathies referred from outpatient clinic of Cardiology at Al-Hussein University hospital from November 2018 to July 2019. Results: all patients showed mild to moderate mitral regurge (100% of cases), tricuspid regurge was seen in 3 cases (75% of cases) and aortic regurge was seen in 4 cases (50 % of cases). The most value of MRI study of these patients was to differentiate whether if heart failure is related to 1ry dilated cardiomyopathy or other causes such as ischemia as they have different management in each group. Conclusion: CMR is a valuable (minimally or non-invasive) imaging technique in patients with suspected or known to have non-ischemic cardiomyopathies. It helps to identify the underlying cause, predict prognosis and responsiveness to therapy and affect management as well follow-up and most recently as primary prevention diagnostic tool.

Exenatide promotes cardiac lncRNAs HOX transcript antisense RNA (HOTAIR) in Wistar rats with liver cirrhosis; a novel role of GLP-1 receptor agonists in cirrhotic cardiomyopathy

Long acting non-coding RNAs lncRNAs HOX Transcript Antisense RNA (HOTAIR) is cardioprotective and mediates its effect through sirtulin 1 (SIRT1). The decrease in HOTAIR expression predisposes to various types of cardiomyopathy. We aimed to investigate whether decrease HOTAIR expression is involved in cirrhotic cardiomyopathy or not and the role of glucagon like peptide 1 receptor (GLP-1 receptor) in facilitating its effect through studying the effect of a exenatide (EXA), on cardiac function as well as the expression of some relevant bio-molecules. Rats were used and divided into: naïve, EXA, Thioacetamide (TAA) and TAA + EXA groups. ECG, dobutamine stress test (DST) were done. AST, ALT, fasting blood glucose, troponin I were measured. Cardiac HOTAIR & SIRT1, hepatic and cardiac GLP-1 receptor expression levels were investigated in addition to histological studies. Our results showed that EXA administration in control rats produced no significant changes. TAA induced cirrhosis with insulin resistance and significant changes in cardiac functions. GLP-1 receptor, HOTAIR and SIRT1 expression in cardiac tissue were significantly decreased with a significant increase in troponin I. EXA + TAA group showed a restoration of the hepatic architecture and function. EXA treatment produced significant improvement in cardiac parameters and was associated with increasing the expression of cardiac GLP-1 receptor, HOTAIR. The cardiac muscle showed an apparent decrease in collagen fibers. So we can conclude that EXA promotes the protective effect of HOTAIR on cardiac structure and function in rat model of cirrhosis which may introduce a new therapeutic strategy in cirrhotic cardiomyopathy.

Non-familial cardiomyopathies in Lebanon: exome sequencing results for five idiopathic cases

BackgroundCardiomyopathies affect more than 0.5% of the general population. They are associated with high risk of sudden cardiac death, which can result from either heart failure or electrical abnormalities. Although different mechanisms underlie the various types of cardiomyopathies, a principal pathology is common to all and is usually at the level of the cardiac muscle. With a relatively high incidence rate in most countries, and a subsequent major health burden on both the families and governments, cardiomyopathies are gaining more attention by researchers and pharmaceutical companies as well as health government bodies. In Lebanon, there is no official data about the spectrum of the diseases in terms of their respective prevalence, clinical, or genetic profiles.MethodsWe used exome sequencing to unravel the genetic basis of idiopathic cases of cardiomyopathies in Lebanon, a relatively small country with high rates of consanguineous marriages.ResultsFive cases were diagnosed with different forms of cardiomyopathies, and exome sequencing revealed the presence of already documented or novel mutations in known genes in three cases: LMNA for an Emery Dreifuss Muscular Dystrophy case, PKP2 for an arrhythmogenic right ventricle dysplasia case, and MYPN for a dilated cardiomyopathy case. Interestingly two brothers with hypertrophic cardiomyopathy have a novel missense variation in NPR1, the gene encoding the natriuretic peptides receptor type I, not reported previously to be causing cardiomyopathies.ConclusionOur results unravel novel mutations in known genes implicated in cardiomyopathies in Lebanon. Changes in clinical management however, require genetic profiling of a larger cohort of patients.