J. Cardiovasc. Dev. Dis.2015, 2(3), 141-164; doi:10.3390/jcdd2030141 - published 25 June 2015 Show/Hide Abstract
Abstract: Calcium phosphate (CaP) crystals are formed in pathological calcification as well as during stone formation. Although there are several theories as to how these crystals can develop through the combined interactions of biochemical and biophysical factors, the exact mechanism of such mineralization is largely unknown. Based on the published scientific literature, we found that common factors can link the initial stages of stone formation and calcification in anatomically distal tissues and organs. For example, changes to the spatiotemporal conditions of the fluid flow in tubular structures may provide initial condition(s) for CaP crystal generation needed for stone formation. Additionally, recent evidence has provided a meaningful association between the active participation of proteins and transcription factors found in the bone forming (ossification) mechanism that are also involved in the early stages of kidney stone formation and arterial calcification. Our review will focus on three topics of discussion (physiological influences—calcium and phosphate concentration—and similarities to ossification, or bone formation) that may elucidate some commonality in the mechanisms of stone formation and calcification, and pave the way towards opening new avenues for further research.
J. Cardiovasc. Dev. Dis.2015, 2(2), 125-140; doi:10.3390/jcdd2020125 - published 2 June 2015 Show/Hide Abstract
Abstract: There is an urgent quest for improved heart health. Here, we review how neutron radiation can provide insight into the molecular basis of heart health. Lower cholesterol, a daily intake of aspirin and supplemental vitamin E are argued to all improve heart health. However, the mechanisms behind these common regimens, and others, are not entirely understood. It is not clear why a daily intake of aspirin can help some people with heart disease, and the benefits of vitamin E in the treatment of reperfusion injury have been heavily debated. The molecular impact of cholesterol in the body is still a hot topic. Neutron scattering experiments present a unique opportunity for biophysicists attempting to address these problems. We review some recently published studies that are advancing our understanding of how cholesterol, vitamin E and aspirin work at the molecular level, by studying the impact of these molecules on the cell membrane. These insights engage the broader health science community with new ways of thinking about these molecules.
J. Cardiovasc. Dev. Dis.2015, 2(2), 108-124; doi:10.3390/jcdd2020108 - published 15 May 2015 Show/Hide Abstract
Abstract: Cardiac valve structure and function are primarily determined during early development. Consequently, abnormally-formed heart valves are the most common type of congenital heart defects. Several adult valve diseases can be backtracked to abnormal valve development, making it imperative to completely understand the process and regulation of heart valve development. Epithelial-to-mesenchymal transition (EMT) plays an important role in the development of heart valves. Though hemodynamics is vital to valve development, its role in regulating EMT is still unknown. In this study, intracardiac hemodynamics were altered by constricting the outflow tract (OFT)/ventricle junction (OVJ) of HH16–17 (Hamilton and Hamburger (HH) Stage 16–17) chicken embryos, ex ovo for 24 h. The constriction created an increase in peak and time-averaged centerline velocity along the OFT without changes to volumetric flow or heart rate. Computational fluid dynamics was used to estimate the level of increased spatially-averaged wall shear stresses on the OFT cushion from AMIRA reconstructions. OFT constriction led to a significant decrease in OFT cushion volume and the number of invaded mesenchyme in the OFT cushion. qPCR analysis revealed altered mRNA expression of a representative panel of genes, vital to valve development, in the OFT cushions from banded hearts. This study indicates the importance of hemodynamics in valve development.
J. Cardiovasc. Dev. Dis.2015, 2(2), 93-107; doi:10.3390/jcdd2020093 - published 13 May 2015 Show/Hide Abstract
Abstract: Electrocardiogram (ECG)-based detection of left ventricular systolic dysfunction (LVSD) has poor specificity and positive predictive value, even when including major ECG abnormalities, such as left bundle branch block (LBBB) within the criteria for diagnosis. Although machine-read ECG algorithms do not provide information on LVSD, advanced ECG (A-ECG), using multiparameter scores, has superior diagnostic utility to strictly conventional ECG for identifying various cardiac pathologies, including LVSD. Methods: We evaluated the diagnostic utility of A-ECG in a case-control study of 40 patients with LVSD (LV ejection fraction < 50% by echocardiography), due to non-ischemic cardiomyopathy (NICM), and 39 other patients without LVSD. Diagnostic sensitivity and specificity for LVSD were determined after applying a previously validated probabilistic A-ECG score for LVSD to stored standard (10 s) clinical 12L ECGs. In 25 of the NICM patients who had serial ECGs and echocardiograms, changes in the A-ECG score versus in echocardiographic LV ejection fraction were also studied to determine the level of agreement between the two tests. Results: Analyses by A-ECG had a sensitivity of 95% for LVSD (93% if excluding N = 11 patients with LBBB) and specificity of 95%. In the 29 NICM patients without LBBB who had serial ECGs, sensitivity improved to 97% when all ECGs were considered. By comparison, human readers in a busy clinical environment had a sensitivity of 90% and specificity of 63%. A-ECG score trajectories demonstrated improvement, deterioration or no change in LVSD, which agreed with echocardiography, in 76% of cases (n = 25). Conclusion: A-ECG scoring detects LVSD due to NICM with high sensitivity and specificity. Serial A-ECG score trajectories also represent a method for inexpensively demonstrating changes in LVSD. A-ECG scoring may be of particular value in areas where echocardiography is unavailable, or as a gatekeeper for echocardiography.
J. Cardiovasc. Dev. Dis.2015, 2(2), 76-92; doi:10.3390/jcdd2020076 - published 29 April 2015 Show/Hide Abstract
Abstract: Cardiovascular malformations (CVMs) are the most common birth defect, occurring in 1%–5% of all live births. Although the genetic contribution to CVMs is well recognized, the genetic causes of human CVMs are identified infrequently. In addition, a failure of systematic deep phenotyping of CVMs, resulting from the complexity and heterogeneity of malformations, has obscured genotype-phenotype correlations and contributed to a lack of understanding of disease mechanisms. To address these knowledge gaps, we have developed the Cytogenomics of Cardiovascular Malformations (CCVM) Consortium, a multi-site alliance of geneticists and cardiologists, contributing to a database registry of submicroscopic genetic copy number variants (CNVs) based on clinical chromosome microarray testing in individuals with CVMs using detailed classification schemes. Cardiac classification is performed using a modification to the National Birth Defects Prevention Study approach, and non-cardiac diagnoses are captured through ICD-9 and ICD-10 codes. By combining a comprehensive approach to clinically relevant genetic analyses with precise phenotyping, the Consortium goal is to identify novel genomic regions that cause or increase susceptibility to CVMs and to correlate the findings with clinical phenotype. This registry will provide critical insights into genetic architecture, facilitate genotype-phenotype correlations, and provide a valuable resource for the medical community.
J. Cardiovasc. Dev. Dis.2015, 2(2), 66-75; doi:10.3390/jcdd2020066 - published 24 April 2015 Show/Hide Abstract
Abstract: Background/Aim: It is still controversial whether tighter glycemic control is associated with better clinical outcomes in patients with kidney failure. We examined the association between glucose serum concentrations and cardiovascular disease in patients on the end stage of renal disease without diabetes mellitus. Methods: We studied 76 patients on on-line hemodiafiltration. Cardiovascular disease was defined by the existence of coronary disease (CD). Arterial stiffness was measured as carotid-femoral pulse wave velocity (c-fPWV) and carotid augmentation index (AIx). The concentrations of beta2-microglobulin (β2M) and insulin were measured by radioimmunoassays and insulin resistance by HOMA-IR. We built a logistic-regression analysis to examine the role of glucose on cardiovascular disease after adjustment for the traditional and specific risk factors for dialysis patients. Results: Serum glucose was positively correlated with beta2M, insulin and HOMA-IR (r = 0.361, p = 0.002, r = 0.581, p = 0.001 and r = 0.753, p = 0.001 respectively). Logistic-regression analysis did not show significant impact of glucose concentrations on cardiovascular disease after adjustment for traditional and specific risk factors. Conclusions: The association between elevated glucose serum concentrations and represented by coronary syndrome cardiovascular disease in patients on the end stage of renal disease without diabetes mellitus was not found significant.