J. Cardiovasc. Dev. Dis.2014, 1(3), 201-213; doi:10.3390/jcdd1030201 - published 10 October 2014 Show/Hide Abstract
Abstract: Despite gaining focus, cardiovascular disease (CVD) remains the leading cause of death worldwide. Health promotion agencies have traditionally recommended diets that are low in fat in order to reduce CVD risk however, much debate remains about which dietary approaches are the most efficient for effective disease prevention. Common markers of CVD include elevated plasma triglycerides (TG) and low-density lipoprotein (LDL) cholesterol levels, as well as reduced high-density lipoprotein (HDL) cholesterol levels. While weight loss alone can significantly reduce markers of CVD, manipulating dietary macronutrient content contributes to the beneficial effects of weight loss and furthers the improvement of lipid profiles even without the alteration of total caloric intake. Considering the recent attention to diets that are low in carbohydrates rather than fat, it remains to be elucidated the beneficial effects of each diet type when establishing new recommendations for CVD prevention. This review aims to examine the effects of different macronutrient compositions on lipid markers, thus providing insight into the potential roles of various diet types in the targeted prevention against CVD.
J. Cardiovasc. Dev. Dis.2014, 1(3), 177-200; doi:10.3390/jcdd1030177 - published 30 September 2014 Show/Hide Abstract
Abstract: There is considerable confusion as to how best describe the components of the arterial valves. It is hardly surprising, therefore, that similar uncertainties apply to concepts for their development. In this review, we describe the anatomy of the arterial valves as seen in the postnatal heart. We suggest that their working components are best described as leaflets, housed in supporting arterial sinuses. The roots surrounding the leaflets, which are hinged in semilunar fashion, can then be defined as extending from a virtual ring at their base to the sinutubular junction. We also discuss the problems related to definition of the valvar “annulus”. Understanding the development of the arterial roots, which are formed in the central part of the embryonic outflow tract, is facilitated by considering the outflow tract itself as possessing three components, as opposed to the traditional “conus” and “truncus”. These three parts can be described as being distal, intermediate, and proximal. The distal part is separated to form the intrapericardial arterial trunks, while the proximal part becomes the ventricular outflow tracts. It is the intermediate component that houses the developing arterial valves, and their supporting valvar sinuses. The distal parts of the cushions that separate the outflow tract into aortic and pulmonary components, along with the intercalated cushions, excavate to form the leaflets. The walls of the sinuses are formed by growth of non-myocardial tissues from the heart-forming area. We then show how these features can be used to interpret the anatomy and development of congenitally malformed arterial valves.
J. Cardiovasc. Dev. Dis.2014, 1(2), 163-176; doi:10.3390/jcdd1020163 - published 23 September 2014 Show/Hide Abstract
Abstract: Heart valves are complex structures composed of a heterogeneous population of valve interstitial cells (VICs), an overlying endothelium and highly organized layers of extracellular matrix. Alterations in valve homeostasis are characteristic of dysfunction and disease, however the mechanisms that initiate and promote valve pathology are poorly understood. Advancements have been largely hindered by the limited availability of tools for gene targeting in heart valve structures during embryogenesis and after birth. We have previously shown that the transcription factors Sox9 and Scleraxis (Scx) are required for heart valve formation and in this study we describe the recombination patterns of Sox9- and Scx-Cre lines at differential time points in aortic and mitral valve structures. In ScxCre; ROSA26GFP mice, recombination is undetected in valve endothelial cells (VECs) and low in VICs during embryogenesis. However, recombination increases in VICs from post natal stages and by 4 weeks side-specific patterns are observed. Using the inducible Sox9CreERT2 system, we observe recombination in VECs and VICs in the embryo, and high levels are maintained through post natal and juvenile stages. These Cre-drivers provide the field with new tools for gene targeting in valve cell lineages during differential stages of embryonic and post natal maturation and maintenance.
J. Cardiovasc. Dev. Dis.2014, 1(2), 146-162; doi:10.3390/jcdd1020146 - published 26 August 2014 Show/Hide Abstract
Abstract: There is continued debate regarding the appropriate cell type to replace valvular interstitial cells (VICs) in tissue engineered heart valves (TEHVs), particularly for pediatric patients. In this work, neonatal human dermal fibroblasts (nhDFFs) were compared to human pediatric VICs (hpVICs), based on their phenotypic and gene expression characteristics when cultured on collagen type I, fibronectin, fibrin, and tissue culture polystyrene (TCP) substrates. Similar confluency was achieved over the culture period on collagen and fibronectin between both cell types, although nhDFFs tended to reach lower confluence on collagen than on any other substrate. Morphologically, hpVICs tended to spread and form multiple extensions, while nhDFFs remained homogenously spindle-shaped on all substrates. PCR results indicated that fibroblasts did not differ significantly from VICs in gene expression when cultured on fibrin, whereas on collagen type I and fibronectin they showed increased α-SMA, xylosyltransferase I, and collagen type I expression (p < 0.05). However, protein expression of these targets, analyzed by immunocytochemistry and Western blotting, was not significantly different between cell types. These results suggest that nhDFFs express similar matrix production and remodeling genes as hpVICs, and the choice of substrate for TEHV construction can affect the growth and expression profile of nhDFFs as compared to native hpVICs.
J. Cardiovasc. Dev. Dis.2014, 1(1), 134-145; doi:10.3390/jcdd1010134 - published 22 May 2014 Show/Hide Abstract
Abstract: Congenital heart disease (CHD) affects the intricate structure and function of the heart and is one of the leading causes of death in newborns. The genetic basis of CHD is beginning to emerge. Our laboratory has been engaged in identifying mutations in genes linked to CHD both in families and in sporadic cases. Over the last two decades, we have employed linkage analysis, targeted gene sequencing and genome wide association studies to identify genes involved in CHDs. Cardiac specific genes that encode transcription factors and sarcomeric proteins have been identified and linked to CHD. Functional analysis of the relevant mutant proteins has established the molecular mechanisms of CHDs in our studies.
J. Cardiovasc. Dev. Dis.2014, 1(1), 121-133; doi:10.3390/jcdd1010121 - published 21 May 2014 Show/Hide Abstract
Abstract: 3'-5'-cyclic adenosine monophosphate (cAMP) is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs). Initially, it was thought that protein kinase A (PKA) exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC) and hyperpolarizing cyclic nucleotide-gated (HCN) channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc) genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins.