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J. Cardiovasc. Dev. Dis., Volume 3, Issue 1 (March 2016) – 10 articles

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Review
Probing the Electrophysiology of the Developing Heart
J. Cardiovasc. Dev. Dis. 2016, 3(1), 10; https://doi.org/10.3390/jcdd3010010 - 22 Mar 2016
Cited by 4 | Viewed by 3128
Abstract
Many diseases that result in dysfunction and dysmorphology of the heart originate in the embryo. However, the embryonic heart presents a challenging subject for study: especially challenging is its electrophysiology. Electrophysiological maturation of the embryonic heart without disturbing its physiological function requires the [...] Read more.
Many diseases that result in dysfunction and dysmorphology of the heart originate in the embryo. However, the embryonic heart presents a challenging subject for study: especially challenging is its electrophysiology. Electrophysiological maturation of the embryonic heart without disturbing its physiological function requires the creation and deployment of novel technologies along with the use of classical techniques on a range of animal models. Each tool has its strengths and limitations and has contributed to making key discoveries to expand our understanding of cardiac development. Further progress in understanding the mechanisms that regulate the normal and abnormal development of the electrophysiology of the heart requires integration of this functional information with the more extensively elucidated structural and molecular changes. Full article
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Article
TLR-4 and CD14 Genotypes and Soluble CD14: Could They Predispose to Coronary Atherosclerosis?
J. Cardiovasc. Dev. Dis. 2016, 3(1), 9; https://doi.org/10.3390/jcdd3010009 - 10 Mar 2016
Cited by 4 | Viewed by 2150
Abstract
Background: Inflammatory mechanisms are key to the pathogenesis of atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD). Methods: DNA was obtained from 100 [...] Read more.
Background: Inflammatory mechanisms are key to the pathogenesis of atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD). Methods: DNA was obtained from 100 human paraffin-embedded aortic specimens, from cadavers with known coronary atheromatosis (Group A) and 100 blood samples from patients with CAD, as detected by cardiac Multi-Detector-row-Computed-Tomography (MDCT) (Group B). Our control group consisted of 100 healthy individuals (Group C). Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR). Plasma levels of sCD14 were measured with ELISA. Results: For TLR-4 Asp299Gly and Thr399Ile polymorphisms, no statistically significant differences were observed. Regarding the C260T polymorphism, frequencies of T allele were significantly higher in the control group compared to the case group (p = 0.05). The Odds Ratio (OR) showed statistically significant association of TT genotype with healthy individuals (OR 0.25, 95% Confidence Interval CI 0.10–0.62, p = 0.0017). Plasma levels of sCD14 in patients with CAD (mean value = 1.35 μg/mL) were reduced when compared to reference value. Conclusions: The studied polymorphisms ofTLR-4 showed no association with CAD. Conversely, the functional polymorphism of CD14 has a statistically significant difference in expression between healthy and affected by CAD individuals. Full article
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Article
Factors Affecting Hypertension among the Malaysian Elderly
J. Cardiovasc. Dev. Dis. 2016, 3(1), 8; https://doi.org/10.3390/jcdd3010008 - 02 Mar 2016
Cited by 9 | Viewed by 3862
Abstract
Hypertension is a common chronic disease in the elderly. This study aimed to determine the effects of age, ethnicity, gender, education, marital status, nutritional parameters, and blood elements on the risk of high blood pressure in the Malaysian elderly. This research was conducted [...] Read more.
Hypertension is a common chronic disease in the elderly. This study aimed to determine the effects of age, ethnicity, gender, education, marital status, nutritional parameters, and blood elements on the risk of high blood pressure in the Malaysian elderly. This research was conducted on a group of 2322 non-institutionalized Malaysian elderly. The hierarchy binary logistic regression analysis was applied to estimate the risk of hypertension in respondents. Approximately, 45.61% of subjects had hypertension. The findings indicated that the female gender (Odds ratio (OR) = 1.54), an increase in body weight (OR = 1.61), and an increase in the blood levels of albumin (OR = 1.51), glucose (OR = 1.92), and triglycerides (OR = 1.27) significantly increased the risk of hypertension in subjects (p < 0.05). Conversely, an increase in both dietary carbohydrates (OR = 0.74), and blood cholesterol level (OR = 0.42) significantly reduced the risk of hypertension in samples (p < 0.05). Furthermore, the results showed that ethnicity was a non-relevant factor to increase the risk of hypertension in subjects. It was concluded that female gender, an increase in body weight, and an increase in the blood levels of glucose, triglycerides, and albumin enhanced the risk of high blood pressure in the Malaysian elderly. In addition, an increase in both dietary carbohydrates and blood cholesterol level decreased hypertension in subjects. Full article
Review
Drosophila in the Heart of Understanding Cardiac Diseases: Modeling Channelopathies and Cardiomyopathies in the Fruitfly
J. Cardiovasc. Dev. Dis. 2016, 3(1), 7; https://doi.org/10.3390/jcdd3010007 - 18 Feb 2016
Cited by 7 | Viewed by 3175
Abstract
Cardiovascular diseases and, among them, channelopathies and cardiomyopathies are a major cause of death worldwide. The molecular and genetic defects underlying these cardiac disorders are complex, leading to a large range of structural and functional heart phenotypes. Identification of molecular and functional mechanisms [...] Read more.
Cardiovascular diseases and, among them, channelopathies and cardiomyopathies are a major cause of death worldwide. The molecular and genetic defects underlying these cardiac disorders are complex, leading to a large range of structural and functional heart phenotypes. Identification of molecular and functional mechanisms disrupted by mutations causing channelopathies and cardiomyopathies is essential to understanding the link between an altered gene and clinical phenotype. The development of animal models has been proven to be efficient for functional studies in channelopathies and cardiomyopathies. In particular, the Drosophila model has been largely applied for deciphering the molecular and cellular pathways affected in these inherited cardiac disorders and for identifying their genetic modifiers. Here we review the utility and the main contributions of the fruitfly models for the better understanding of channelopathies and cardiomyopathies. We also discuss the investigated pathological mechanisms and the discoveries of evolutionarily conserved pathways which reinforce the value of Drosophila in modeling human cardiac diseases. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Article
Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish
J. Cardiovasc. Dev. Dis. 2016, 3(1), 6; https://doi.org/10.3390/jcdd3010006 - 26 Jan 2016
Cited by 5 | Viewed by 3378
Abstract
Animal models have played a critical role in validating human dilated cardiomyopathy (DCM) genes, particularly those that implicate novel mechanisms for heart failure. However, the disease phenotype may be delayed due to age-dependent penetrance. For this reason, we generated an adult zebrafish model, [...] Read more.
Animal models have played a critical role in validating human dilated cardiomyopathy (DCM) genes, particularly those that implicate novel mechanisms for heart failure. However, the disease phenotype may be delayed due to age-dependent penetrance. For this reason, we generated an adult zebrafish model, which is a simpler vertebrate model with higher throughput than rodents. Specifically, we studied the zebrafish homologue of GATAD1, a recently identified gene for adult-onset autosomal recessive DCM. We showed cardiac expression of gatad1 transcripts, by whole mount in situ hybridization in zebrafish embryos, and demonstrated nuclear and sarcomeric I-band subcellular localization of Gatad1 protein in cardiomyocytes, by injecting a Tol2 plasmid encoding fluorescently-tagged Gatad1. We next generated gatad1 knock-out fish lines by TALEN technology and a transgenic fish line that expresses the human DCM GATAD1-S102P mutation in cardiomyocytes. Under stress conditions, longitudinal studies uncovered heart failure (HF)-like phenotypes in stable KO mutants and a tendency toward HF phenotypes in transgenic lines. Based on these efforts of studying a gene-based inherited cardiomyopathy model, we discuss the strengths and bottlenecks of adult zebrafish as a new vertebrate model for assessing candidate cardiomyopathy genes. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Editorial
Acknowledgement to Reviewers of Journal of Cardiovascular Development and Disease in 2015
J. Cardiovasc. Dev. Dis. 2016, 3(1), 5; https://doi.org/10.3390/jcdd3010005 - 26 Jan 2016
Viewed by 1556
Abstract
The editors of Journal of Cardiovascular Development and Disease would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...] Full article
Reply
Response to Ponamgi et al. Comments on Khalighi et al. Takotsubo Cardiomyopathy: A Long Term Follow-up Shows Benefit with Risk Factor Reduction. J. Cardiovasc. Dev. Dis., 2015, 2, 273–281.
J. Cardiovasc. Dev. Dis. 2016, 3(1), 4; https://doi.org/10.3390/jcdd3010004 - 26 Jan 2016
Viewed by 1602
Abstract
We appreciate the thorough response given by Ponagmi et al. [1], who rightly point out that the pathophysiology and modifiable risk factors of Takotsubo Cardiomyopathy (TC) have yet to be unequivocally established. [...] Full article
Comment
Long-term Benefits of Risk Factor Reduction in Takotsubo Cardiomyopathy.—A Comment on Khalighi et al. Entitled “Takotsubo Cardiomyopathy: A Long Term Follow-up Shows Benefit with Risk Factor Reduction”, J. Cardiovasc. Dev. Dis., 2015, 2, 273–281.
J. Cardiovasc. Dev. Dis. 2016, 3(1), 3; https://doi.org/10.3390/jcdd3010003 - 25 Jan 2016
Cited by 2 | Viewed by 1507
Abstract
Takotsubo cardiomyopathy (TC) or stress-induced cardiomyopathy is also popularly referred to as “broken heart syndrome” or “apical ballooning syndrome”. [...] Full article
Article
Segregation of Central Ventricular Conduction System Lineages in Early SMA+ Cardiomyocytes Occurs Prior to Heart Tube Formation
J. Cardiovasc. Dev. Dis. 2016, 3(1), 2; https://doi.org/10.3390/jcdd3010002 - 21 Jan 2016
Cited by 8 | Viewed by 2973
Abstract
The cardiac conduction system (CCS) transmits electrical activity from the atria to the ventricles to coordinate heartbeats. Atrioventricular conduction diseases are often associated with defects in the central ventricular conduction system comprising the atrioventricular bundle (AVB) and right and left branches (BBs). Conducting [...] Read more.
The cardiac conduction system (CCS) transmits electrical activity from the atria to the ventricles to coordinate heartbeats. Atrioventricular conduction diseases are often associated with defects in the central ventricular conduction system comprising the atrioventricular bundle (AVB) and right and left branches (BBs). Conducting and contractile working myocytes share common cardiomyogenic progenitors, however the time at which the CCS lineage becomes specified is unclear. In order to study the fate and the contribution to the CCS of cardiomyocytes during early heart tube formation, we performed a genetic lineage analysis using a Sma-CreERT2 mouse line. Lineage tracing experiments reveal a sequential contribution of early Sma expressing cardiomyocytes to different cardiac compartments, labeling at embryonic day (E) 7.5 giving rise to the interventricular septum and apical left ventricular myocardium. Early Sma expressing cardiomyocytes contribute to the AVB, BBs and left ventricular Purkinje fibers. Clonal analysis using the R26-confetti reporter mouse crossed with Sma-CreERT2 demonstrates that early Sma expressing cardiomyocytes include cells exclusively fated to give rise to the AVB. In contrast, lineage segregation is still ongoing for the BBs at E7.5. Overall this study highlights the early segregation of the central ventricular conduction system lineage within cardiomyocytes at the onset of heart tube formation. Full article
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Article
Effect of Outflow Tract Banding on Embryonic Cardiac Hemodynamics
J. Cardiovasc. Dev. Dis. 2016, 3(1), 1; https://doi.org/10.3390/jcdd3010001 - 24 Dec 2015
Cited by 15 | Viewed by 2635
Abstract
We analyzed heart wall motion and blood flow dynamics in chicken embryos using in vivo optical coherence tomography (OCT) imaging and computational fluid dynamics (CFD) embryo-specific modeling. We focused on the heart outflow tract (OFT) region of day 3 embryos, and compared normal [...] Read more.
We analyzed heart wall motion and blood flow dynamics in chicken embryos using in vivo optical coherence tomography (OCT) imaging and computational fluid dynamics (CFD) embryo-specific modeling. We focused on the heart outflow tract (OFT) region of day 3 embryos, and compared normal (control) conditions to conditions after performing an OFT banding intervention, which alters hemodynamics in the embryonic heart and vasculature. We found that hemodynamics and cardiac wall motion in the OFT are affected by banding in ways that might not be intuitive a priori. In addition to the expected increase in ventricular blood pressure, and increase blood flow velocity and, thus, wall shear stress (WSS) at the band site, the characteristic peristaltic-like motion of the OFT was altered, further affecting flow and WSS. Myocardial contractility, however, was affected only close to the band site due to the physical restriction on wall motion imposed by the band. WSS were heterogeneously distributed in both normal and banded OFTs. Our results show how banding affects cardiac mechanics and can lead, in the future, to a better understanding of mechanisms by which altered blood flow conditions affect cardiac development leading to congenital heart disease. Full article
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