Pathological Conditions Of Heart Research Articles

Role of Trace Elements in Heart Failure

This study more on the role of trace elements such as iron(Fe), zinc(Zn), chromium(Cr), manganese(Mn), copper(Cu), cobalt(Co), selenium(sn) on the medicinal conditions like heart failure, myocardial infarction, cardiomyopathy, congestive heart failure, pericardial effusion, keshan’s disease and various other cardiovascular diseases. This study highlights the levels of individual trace elements or the elements which are present in minute quantities either it is a deficiency or in excess which can lead to various different cardiac diseases such mainly focusing on heart failure. it also stresses on the side of heart failure as it may be right-sided or left sided based on the location of deficiency. In an averagely built human adult, 0.02percent constitute of eleven essential trace elements. It also discusses that inadequate consumption of these minor elements via diet may lead to pathological conditions of heart. This study also throws light on the classification of trace elements given by Frieden in 1981,broadly classified as micro elements, trace elements, and ultra-trace elements on the basis of amount detected in tissues of averagely built human adult , further trace elements are classified as essential trace elements, probable essential trace elements, physically beneficial trace elements, .the basic pathophysiology and etiology is also given which can lead to heart failure and various other cardiovascular diseases or conditions. Diagnosis of various diseases can be made by monitoring the levels of various trace elements and it can also help to reduce the risk of having heart related medicinal conditions by including these minor elements in diet so as to improve the operating condition of heart this study also focuses on the dietary sources of trace elements. Cardiovascular emergency can also be avoided by continuous monitoring of subjects who are at high risk.

Efficient Ventricular Parameter Estimation Using AI-Surrogate Models.

The onset and progression of pathological heart conditions, such as cardiomyopathy or heart failure, affect its mechanical behaviour due to the remodelling of the myocardial tissues to preserve its functional response. Identification of the constitutive properties of heart tissues could provide useful biomarkers to diagnose and assess the progression of disease. We have previously demonstrated the utility of efficient AI-surrogate models to simulate passive cardiac mechanics. Here, we propose the use of this surrogate model for the identification of myocardial mechanical properties and intra-ventricular pressure by solving an inverse problem with two novel AI-based approaches. Our analysis concluded that: (i) both approaches were robust toward Gaussian noise when the ventricle data for multiple loading conditions were combined; and (ii) estimates of one and two parameters could be obtained in less than 9 and 18 s, respectively. The proposed technique yields a viable option for the translation of cardiac mechanics simulations and biophysical parameter identification methods into the clinic to improve the diagnosis and treatment of heart pathologies. In addition, the proposed estimation techniques are general and can be straightforwardly translated to other applications involving different anatomical structures.

Glucose fluctuation accelerates cardiac injury of diabetic mice via sodium-dependent glucose cotransporter 1 (SGLT1)

Recent studies have shown that blood glucose fluctuation is associated with complications of diabetes mellitus (DM). SGLT1 (sodium-dependent glucose cotransporter 1), is highly expressed in pathological conditions of heart, and is expressed in cardiomyocytes induced by high glucose. Herein, we constructed a diabetic mouse model with glucose fluctuation to investigate whether SGLT1 is involved in glucose fluctuation-induced cardiac injury. Echocardiography, histology examination, and TUNEL staining were performed to evaluate cardiac dysfunction and damage. To assess glucose fluctuation-induced oxidative stress, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. To assess mitochondrial dysfunction, mitochondrial membrane potential (MMP), ATP content, mitochondrial respiratory chain complex activity, and expression of mitochondrial fusion and fission proteins were determined. The results indicated that diabetic mice with glucose fluctuation showed elevation of cardiac SGLT1 expression, left ventricular dysfunction, oxidative stress and mitochondrial dysfunction. Knockdown of SGLT1 could abrogate the effects of glucose fluctuation on cardiac injury. Thus, our study highlighted that SGLT1 plays an important role in glucose fluctuation induced cardiac injury through oxidative stress and mitochondrial dysfunction.

TRICking SOCE into altered oscillations

Defective ER/SR-cytosol Ca2+ cycling is associated with increased ER stress, pathological heart conditions and muscular defects. Within the SR, ryanodine receptor 2 (RyR2) is required for excitation/contraction coupling. Ca2+ release from the SR is counterbalanced by K+ influx through trimeric intracellular cation (TRIC) channels to maintain ER/SR polarity. New functions of TRIC channels have been discovered.

Age-related histomorphometric and immunohistochemical changes of the moderator band in Egyptian Baladi cattle.

The moderator band (MB) is a common fibromuscular anatomical structure for the right ventricle of most animals. The histomorphometric and immunohistochemical analysis of the MBs of Egyptian Baladi cattle in relation to age was the aim of this study. Eighteen clinically healthy animals of both sexes were used for this study. The animals were divided into three groups depending on age, group I (N=4, <1year), group II (N=8, 1-2years) and group III (N=6, 4-8years). Cross sections of the MBs from all groups were stained with H&E, Masson's trichrome and anti-connexin43 (Cx43) antibody for histological and immunohistochemical examinations. Also, measurements for the thickness of the endocardium of the MB as well as, the wall of its muscular artery were conducted. Bundles of Purkinje fibres (PFs) were identified peripherally in the endocardial layer and among the myocardial fibres in the core of each MB. The infiltration of endocardial adipocytes was the characteristic for MBs of old animals. All morphometric data showed a significant increase with the advancement of age. Immunohistochemical findings revealed the localization and distribution of Cx43 in the PFs and intercalated discs of all examined MBs. However, variation of Cx43 immunoreactivity was found among the groups depending on the age. On the basis of this study, this conclusion of different histomorphometry and Cx43 expression of the MBs in relation to age was drawn. These interesting findings provide further insight into age-related physiological and pathological heart conditions.

An anti-PDGFRβ aptamer for selective delivery of small therapeutic peptide to cardiac cells.

Small therapeutic peptides represent a promising field for the treatment of pathologies such as cardiac diseases. However, the lack of proper target-selective carriers hampers their translation towards a potential clinical application. Aptamers are cell-specific carriers that bind with high affinity to their specific target. However, some limitations on their conjugation to small peptides and the functionality of the resulting aptamer-peptide chimera exist. Here, we generated a novel aptamer-peptide chimera through conjugation of the PDGFRβ-targeting Gint4.T aptamer to MP, a small mimetic peptide that via targeting of the Cavβ2 subunit of the L-type calcium channel (LTCC) can recover myocardial function in pathological heart conditions associated with defective LTCC function. The conjugation reaction was performed by click chemistry in the presence of N,N,N’,N’,N”-pentamethyldiethylenetriamine as a Cu (I) stabilizing agent in a DMSO-free aqueous buffer. When administered to cardiac cells, the Gint4.T-MP aptamer-peptide chimera was successfully internalized in cells, allowing the functional targeting of MP to LTCC. This approach represents the first example of the use of an internalizing aptamer for selective delivery of a small therapeutic peptide to cardiac cells.

The Effects of Aerobic Exercise and Detraining on Left Ventricular Cardiomyocyte Apoptosis

Apoptosis can occur in several pathological heart conditions. Physical exercise, particularly aerobic exercise may reduce apoptosis on cardiomyocytes. Detraining can restore adaptation after exercise. This study aimed to see the effect of aerobic exercise and detraining on left ventricular cardiomyocyte apoptosis using caspase-3 as the parameter.This was an in vivo experimental study on Wistar rats Rattus Novergicus. Rats divided to 8 groups: 4 sedentary control groups: 4-week (C4), 8-week (C4D), 12-week (C12), 16-week control (C12D), and 4 aerobic exercise treatment groups: 4-week (A4) and 12-week (A12), and 4 &amp; 12-week post aerobic exercise treatment followed by 4 weeks detraining (A4D, A12D). Caspase-3 protein in rat left ventricular tissue was identified by immunohistochemistry staining. Data were analized with ANOVA test using SPSS proggramme version 20.Data analysis showed an increase percentage of caspase-3 expression on post-aerobic exercise (A), be compared with conntrol group (C) (A4 65,3%±2,54 vs K4 6,4%±1,78, p&lt;0,001; A12 41,8%±3,21 vs K12 5,7%±0,88, p&lt;0,001; A4D 66,6%±1,89 vs K4D 8,6%±3,60, p&lt;0,001; A12D 45,1%±1,50 vs K12D 7,4%±2,06, p&lt;0,001). Percentage of caspase-3 expression was not different on post-aerobc exercise (A), be compare with detraining group (A4D 66,6%±1,89% vs A4 65,4%±2,54, p=0,484; A12D 45,1%±1,50 vs A12 41,8%±3,21, p=0,063). Percentage of caspase-3 expression on post 4-week aerobic exercise group was higher than post12-week aerobic exercise (A4 65,4%±2,54 vs A12 41,8%±3,21, p&lt;0,001).In conclusion, the aerobic exercise protocol used in this study, was not found to decrease left ventricular cardiomyocyte apoptosis. Detraining did not increase left ventricular cardiomyocyte apoptosis.

ROS-mediated bidirectional regulation of miRNA results in distinct pathologic heart conditions

Under distinct pathological heart conditions, the expression of a single miRNA can display completely opposite patterns. However, the mechanism underlying the bidirectional regulation of a single miRNA and the clinical implications of this regulation remain largely unknown. To address this issue, we examined the regulation of miR-1, one of the most abundant miRNAs in the heart, during cardiac hypertrophy and ischemia/reperfusion (I/R). Our data indicated that different magnitudes and chronicities of ROS levels in cardiomyocytes resulted in differential expression of miR-1, subsequently altering the expression of myocardin. In animal models, the administration of a miR-1 mimic attenuated cardiac hypertrophy by suppressing the transverse aortic constriction-induced increase in myocardin expression, whereas the administration of anti-miR-1 ameliorated I/R-induced cardiac apoptosis and deterioration of heart function. Our findings indicated that a pathologic stimulus such as ROS can bidirectionally alter the expression of miRNA to contribute to the development of pathological conditions exhibiting distinct phenotypes and that the meticulous adjustment of the pathological miRNA levels is required to improve clinical outcomes.

ZebraBeat: a flexible platform for the analysis of the cardiac rate in zebrafish embryos

Heartbeat measurement is important in assesssing cardiac function because variations in heart rhythm can be the cause as well as an effect of hidden pathological heart conditions. Zebrafish (Danio rerio) has emerged as one of the most useful model organisms for cardiac research. Indeed, the zebrafish heart is easily accessible for optical analyses without conducting invasive procedures and shows anatomical similarity to the human heart. In this study, we present a non-invasive, simple, cost-effective process to quantify the heartbeat in embryonic zebrafish. To achieve reproducibility, high throughput and flexibility (i.e., adaptability to any existing confocal microscope system and with a user-friendly interface that can be easily used by researchers), we implemented this method within a software program. We show here that this platform, called ZebraBeat, can successfully detect heart rate variations in embryonic zebrafish at various developmental stages, and it can record cardiac rate fluctuations induced by factors such as temperature and genetic- and chemical-induced alterations. Applications of this methodology may include the screening of chemical libraries affecting heart rhythm and the identification of heart rhythm variations in mutants from large-scale forward genetic screens.

Multiphysics computational models for cardiac flow and virtual cardiography

A multiphysics simulation approach is developed for predicting cardiac flows as well as for conducting virtual echocardiography (ECHO) and phonocardiography (PC) of those flows. Intraventricular blood flow in pathological heart conditions is simulated by solving the three-dimensional incompressible Navier-Stokes equations with an immersed boundary method, and using this computational hemodynamic data, echocardiographic and phonocardiographic signals are synthesized by separate simulations that model the physics of ultrasound wave scattering and flow-induced sound, respectively. For virtual ECHO, a Doppler ultrasound image is reproduced through Lagrangian particle tracking of blood cell particles and application of sound wave scattering theory. For virtual PC, the generation and propagation of blood flow-induced sounds ('hemoacoustics') is directly simulated by a computational acoustics model. The virtual ECHO is applied to reproduce a color M-mode Doppler image for the left ventricle as well as continuous Doppler image for the outflow tract of the left ventricle, which can be verified directly against clinically acquired data. The potential of the virtual PC approach for providing new insights between disease and heart sounds is demonstrated by applying it to modeling systolic murmurs caused by hypertrophic cardiomyopathy.

D230N Mutation in Tropomyosin and R92L Mutation in Cardiac Troponin T have Strikingly Different Impact on Calcium-Regulated Activation of Cardiac Myofilaments

Dilated Cardiomyopathy (DCM) and Familial Hypertrophic Cardiomyopathy (FHC) are pathological heart conditions mainly associated with sarcomeric mutations that lead to contractile dysfunction. Despite the identification of several mutations associated with FHC and DCM, the role of these mutations in pathological cardiac-remodeling is still elusive. Therefore, we studied length-dependent contractile parameters of murine hearts expressing DCM-associated mutation (D230N in alpha-tropomyosin) and FHC-associated mutation (R92L in cTnT). Mechanical studies were carried out on detergent-skinned cardiac muscle fibers at sarcomere length (SL) 1.9 and 2.3 μm. Our preliminary results show that myofilament Ca2+ sensitivity and cooperativity are affected differently in both mutants, irrespective of SL. Ca2+ sensitivity was decreased in the D230N fibers, but increased in R92L fibers. Ca2+-activated maximal tension was unaltered in both examples. Cooperativity of myofilament activation was significantly decreased in R92L fibers and significantly increased in D230N fibers. Our results suggest that single amino acid substitution mutations in Tm (D230N) and TnT (R92L) cause diverse functional effects, which may correlate with varied pathological remodeling. Further mechano-dynamic studies are planned to determine if other aspects of myofilament activation may be involved in the evolution of complications associated with DCM and FHC.

Support Vectors Machine-based identification of heart valve diseases using heart sounds

Taking into account that heart auscultation remains the dominant method for heart examination in the small health centers of the rural areas and generally in primary healthcare set-ups, the enhancement of this technique would aid significantly in the diagnosis of heart diseases. In this context, the present paper initially surveys the research that has been conducted concerning the exploitation of heart sound signals for automated and semi-automated detection of pathological heart conditions. Then it proposes an automated diagnosis system for the identification of heart valve diseases based on the Support Vector Machines (SVM) classification of heart sounds. This system performs a highly difficult diagnostic task (even for experienced physicians), much more difficult than the basic diagnosis of the existence or not of a heart valve disease (i.e. the classification of a heart sound as ‘healthy’ or ‘having a heart valve disease’): it identifies the particular heart valve disease. The system was applied in a representative global dataset of 198 heart sound signals, which come both from healthy medical cases and from cases suffering from the four most usual heart valve diseases: aortic stenosis (AS), aortic regurgitation (AR), mitral stenosis (MS) and mitral regurgitation (MR). Initially the heart sounds were successfully categorized using a SVM classifier as normal or disease-related and then the corresponding murmurs in the unhealthy cases were classified as systolic or diastolic. For the heart sounds diagnosed as having systolic murmur we used a SVM classifier for performing a more detailed classification of them as having aortic stenosis or mitral regurgitation. Similarly for the heart sounds diagnosed as having diastolic murmur we used a SVM classifier for classifying them as having aortic regurgitation or mitral stenosis. Alternative classifiers have been applied to the same data for comparison (i.e. back-propagation neural networks, k-nearest-neighbour and naïve Bayes classifiers), however their performance for the same diagnostic problems was lower than the SVM classifiers proposed in this work.

Semi-automated assessment of left ventricular mass using transaxial Tc-99m Sestamibi SPECT imaging

The “ left ventricular mass” (LVM) using Tc-99m Sestamibi SPECT imaging may be a useful parameter to quantitatively assess the left ventricle and hence its function. The LVM was determined without reorienting the images along the long axis of the left ventricle. A comparison with reoriented SPECT images was then performed. The LVM showed the expected variations among different pathological heart conditions and the control subjects. The left ventricular mass obtained from non-reoriented tomographic views of the myocardium can be a useful index to quantitatively assess various heart conditions where the myocardium lacks perfusion either between rest and stress studies or similar conditions in longitudinal studies.

Potential of Adiponectin as a Cardioprotective Agent

In this review, we focus on the role of adiponectin as a cardioprotective agent in several pathological heart conditions. Obesity is closely associated with Type 2 diabetes, hypertension and heart disease. Adiponectin is an adipose tissue-derived hormone whose concentration is downregulated in subjects with obesity-related diseases. Hypoadiponectinemia has been identified as an independent risk factor for Type 2 diabetes, coronary artery disease, acute coronary syndrome and hypertension. More recent experimental findings have shown that adiponectin directly affects signaling in cardiac myocytes and has beneficial effects on several pathological heart conditions, including cardiac hypertrophy and myocardial infarction. The favorable effects of adiponectin are associated with attenuated inflammatory response, decreased myocyte death, decreased hypertrophic response, maintained ischemia-induced angiogenesis and reduced interstitial fibrosis. Therefore, adiponectin could represent a molecular target for treating obesity-linked cardiac diseases.

Immortalization and Characterization of Porcine Ventricular Endocardial Endothelial Cells

Endocardial endothelial cells (EECs), which form the inner lining of the cavities of the heart, are a distinct cell population whose dysfunction can be critical in pathological conditions of heart. Insights into the role and organization of these cells in pathological states of the heart are limited mainly due to a dearth of experimental models. To date no endocardial endothelial cell line is available. The authors attempted to immortalize porcine ventricular EECs by transfecting the cells with human telomerase reverse transcriptase (hTERT). EECs immortalized by ectopic expression of hTERT exhibit phenotypic and functional characteristics similar to primary EECs. The EE cell line could be useful for the study of mechanisms involved in the interaction of EECs with the underlying myocardium and cardiac interstitium and as useful tools in understanding their role in diseased states of heart.

Cardioprotective Actions of Adiponectin

Adiponectin is a fat-derived hormone, which is downregulated in subjects with obesity-related complications. A number of experimental studies have shown that adiponectin has anti-diabetic and anti-inflammatory characteristics and that adiponectin exerts beneficial effects on the development of insulin resistance and atherosclerosis. Recent experimental findings have shown that adiponectin directly modulates the signalling in the heart and plays a protective role in the development of obesity-linked heart diseases. This article focuses on the beneficial actions of adiponectin on various pathological heart conditions.

Targeting adiponectin for cardioprotection

Adiponectin is an adipose tissue-derived plasma protein which has a reduced concentration in subjects with obesity-related diseases. Adiponectin has antidiabetic and anti-inflammatory characteristics, which lead to beneficial actions on various obesity-linked complications. Recent experimental findings have shown that adiponectin contributes to protection against cardiac remodelling after pressure overload and cardiac injury following ischaemia–reperfusion. Thus, adiponectin could emerge as a potential cardioprotective agent for the treatment of several pathological heart conditions.

Acetoxy drug: Protein transacetylase catalyzed activation of human platelet nitric oxide synthase by polyphenolic peracetates

An enhanced intracellular level of Nitric oxide (NO) is essential to ameliorate several pathological conditions of heart and vasculature necessitating the activation of NOS. We have projected in this report the acetylation of eNOS by polyphenolic peracetates (PA) catalyzed by the novel enzyme acetoxy drug: protein transacetylase (TAase) discovered in our laboratory as an unambiguous way of activating NOS which results in the manifestation of physiological action. The human platelet was chosen as the experimental system in order to validate the aforementioned proposition. PA caused profound irreversible activation of platelet NADPH cytochrome c reductase mediated by TAase. The convincing biochemical evidences are presented to show that PA could cause acetylation of the reductase domain of NOS leading to the activation of eNOS in tune with their specificities to platelet TAase. As a result, the enhanced level of NO due to activation of platelet eNOS by PA was found to inhibit the ADP-induced platelet aggregation. The present studies highlight for the first time the role of PA as the novel potent agent for enhancing the intracellular NO levels.

Murine retrovirus infection and the effect of chronic alcohol consumption: proteomic analysis of cardiac protein expression.

The cardiovascular complications of acquired immunodeficiency syndrome (AIDS) are serious, including the occurrence of pathological heart conditions such as cardiomyopathy. Chronic alcohol consumption accentuates the severity of AIDS and may contribute to the development of cardiomyopathy. The aim of this work was to use a proteomics approach to investigate global alterations in protein expression in a mouse model of AIDS in the presence or absence of chronic alcohol consumption. Cardiac proteins were separated by two-dimensional polyacrylamide gel electrophoresis and quantitative computer analysis was used to evaluate the resulting two-dimensional protein profiles. Proteins that were differentially expressed in the hearts of mice from the different experimental groups were identified by peptide mass finger-printing by matrix-assisted laser desorption/ionization mass spectrometry. A number of specific proteins were observed to be differentially expressed in the mouse heart due to the effect of ethanol feeding alone. Differentially expressed proteins were also observed that were due to viral infection alone. Ethanol feeding and viral infection appeared to have similar effects on the expression of a number of proteins. A total of 24 proteins were altered by infection alone. Of these 24 proteins, eight were affected by alcohol, with six alterations being ameliorated and two being exacerbated by alcohol. Two of these proteins have been identified as the 27 kDa heat-shock protein and mitochondrial long-chain acyl-CoA thioesterase 1. These results suggest that chronic alcohol consumption may exacerbate the effects of viral infection on the heart by lowering the stress response leading to de-protection and further cytotoxic effects.

Downregulation of Thyroid Hormone Receptor Subtype mRNA Levels by Retinoic Acid in Cultured Cardiomyocytes

The thyroid hormone receptors (TR) and the retinoic acid receptors share a high degree of homology and their signaling pathways interplay. Thyroid hormone (T3) is known to be associated with various pathological heart conditions. Retinoids are known to ameliorate symptoms in hyperthyroid patients. The aim of this study was to investigate if retinoic acid (RA) can have any effects on TR in cardiac cells and thus play a role in heart disease. Confluent AT-1 cardiomyocytes were treated with RA, T3 depleted medium and DITPA (a cardiotonic T3 analogue) for 48 hours. Solution hybridization for the determination of mRNA for TR α 1, α 1, β 1and β 2was performed. RA, T3 and DITPA significantly downregulated the α 1, β 1and β 2. The T3 depleted medium did not affect the TR subtypes. The specificity of the solution hybridization method was tested by an RNase protection assay. In conclusion, RA downregulates TR in a similar way as T3 in cardiac cells, indicating a role for RA in thyroid associated heart disease.