scholarly journals GATA4 transgenic mice as an in vivo model of congenital heart disease

2015 ◽  
Vol 35 (6) ◽  
pp. 1545-1553 ◽  
Author(s):  
HUA HAN ◽  
YU CHEN ◽  
GANG LIU ◽  
ZENGQIANG HAN ◽  
ZHOU ZHAO ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Transgenic Mice ◽  
Congenital Heart ◽  
In Vivo Model

scholarly journals High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jun-yi Zhu ◽  
Yulong Fu ◽  
Margaret Nettleton ◽  
Adam Richman ◽  
Zhe Han
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
High Throughput ◽  
Congenital Heart ◽  
De Novo ◽  
Disease Risk ◽  
In Vivo Model ◽  
Disease Genes ◽  
Specific Patient

Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes, including a subgroup encoding histone H3K4 modifying proteins. We also demonstrated the use of Drosophila to evaluate cardiac phenotypes resulting from specific, patient-derived alleles of candidate disease genes. We describe the first high throughput in vivo validation system to screen candidate disease genes identified from patients. This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors.

scholarly journals Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease

2021 ◽  
Vol 14 (3) ◽  
pp. dmm047522
Author(s):  
Abdul Jalil Rufaihah ◽  
Ching Kit Chen ◽  
Choon Hwai Yap ◽  
Citra N. Z. Mattar
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Computational Models ◽  
Developing Heart ◽  
Heterogenous Group ◽  
In Silico Models ◽  
Large Animals

ABSTRACTBirth defects contribute to ∼0.3% of global infant mortality in the first month of life, and congenital heart disease (CHD) is the most common birth defect among newborns worldwide. Despite the significant impact on human health, most treatments available for this heterogenous group of disorders are palliative at best. For this reason, the complex process of cardiogenesis, governed by multiple interlinked and dose-dependent pathways, is well investigated. Tissue, animal and, more recently, computerized models of the developing heart have facilitated important discoveries that are helping us to understand the genetic, epigenetic and mechanobiological contributors to CHD aetiology. In this Review, we discuss the strengths and limitations of different models of normal and abnormal cardiogenesis, ranging from single-cell systems and 3D cardiac organoids, to small and large animals and organ-level computational models. These investigative tools have revealed a diversity of pathogenic mechanisms that contribute to CHD, including genetic pathways, epigenetic regulators and shear wall stresses, paving the way for new strategies for screening and non-surgical treatment of CHD. As we discuss in this Review, one of the most-valuable advances in recent years has been the creation of highly personalized platforms with which to study individual diseases in clinically relevant settings.

Usefulness of multidetector CT imaging to assess vascular stents in children with congenital heart disease: An in vivo and in vitro study

2008 ◽  
Vol 72 (4) ◽  
pp. 544-551 ◽  
Author(s):  
Joachim G. Eichhorn ◽  
Frederick R. Long ◽  
Claudia Jourdan ◽  
Johannes T. Heverhagen ◽  
Sharon L. Hill ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Multidetector Ct ◽  
In Vitro Study ◽  
Ct Imaging ◽  
Vitro Study ◽  
Vascular Stents

scholarly journals Lactobacillus endocarditis with prosthetic material: a case report on non-surgical management with corresponding literature review

2014 ◽  
Vol 6 (3) ◽  
Author(s):  
Mena Botros ◽  
Deepa Mukundan
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Cyanotic Congenital Heart Disease ◽  
Prosthetic Material ◽  
Vancomycin Therapy ◽  
Accurate Identification ◽  
Gram Positive Bacteria ◽  
One Year

<em>Lactobacilli</em> are rod shaped gram positive bacteria that naturally colonize the human gastrointestinal and genitourinary tracts and occasionally cause disease in humans. <em>Lactobacillus</em> infections are found in patients who are immunocompromized or have severe comorbidities. We report <em>Lactobacillus</em> endocarditis in a 17-year-old adolescent girl with cardiac prosthetic material following surgical correction for complex cyanotic congenital heart disease. Accurate identification of the organism can be delayed. Despite <em>in vivo</em> susceptibility to vancomycin, our patient clinically failed vancomycin therapy but ultimately responded to a six-week course of penicillin, in addition to a 4-week course of clindamycin and gentamicin. She recovered without the need for surgical intervention and has been symptom free for one year. Upon review of the literature, we found that <em>Lactobacillus</em> endocarditis has not been reported in a pediatric patient with complex cyanotic congenital heart disease.

scholarly journals In Vivo Pressure-Radius Relationships of the Pulmonary Artery in Children with Congenital Heart Disease

Circulation ◽  
1971 ◽  
Vol 43 (4) ◽  
pp. 585-592 ◽  
Author(s):  
JAY M. M. JARMAKANI ◽  
THOMAS P. GRAHAM ◽  
D. WOODROW BENSON ◽  
RAMON V. CANENT ◽  
JOSEPH C. GREENFIELD
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Artery ◽  
Congenital Heart

Abstract 17061: Impact of Maternal Anxiety on In Vivo Placental Development in Fetuses With Congenital Heart Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yuanchiao Lu ◽  
Kushal Kapse ◽  
Nicole Andersen ◽  
Nickie Andescavage ◽  
Andrea Fry ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Surface Area ◽  
Congenital Heart ◽  
Maternal Anxiety ◽  
Fast Spin Echo ◽  
Single Shot ◽  
Placental Development ◽  
Mean Diameter

Introduction: Studies have shown that maternal stress and anxiety during pregnancy have been associated with a higher incidence of preterm birth and low birth weight. However, the relationship between prenatal maternal mental distress and placental development in fetuses with congenital heart disease (CHD) is unknown. Hypothesis: We tested the hypothesis that elevated maternal anxiety is associated with altered placental morphology in fetuses with CHD. Methods: A total of 141 pregnant women were recruited prospectively (control: 91; two-ventricle/2V CHD: 29; single-ventricle/SV CHD: 21), in which 228 fetal MR scans were performed (gestational age: 31.8±4.5 weeks). Single shot fast spin echo T2-weighted images were acquired on a 1.5 Tesla GE MRI scanner. Placenta tissue was manually segmented, and slice-to-volume registration was used for motion correction and 3D reconstruction. Six placental features were calculated: volume, thickness, elongation, surface area, mean diameter, and umbilical cord centricity. We completed the Spielberger State (SSAI) and Trait (SSAI) Anxiety Inventory at each study visit. Linear mixed models were utilized to analyze the placental features predicted by maternal anxiety. Results: Placental volume, surface area, and mean diameter were decreased with elevated SSAI in 2V CHD fetuses, while volume and cord centricity were increased with higher SSAI in SV CHD fetuses. Lower cord centricity was associated with elevated STAI in 2V CHD fetuses, and elongation was positively associated with STAI in SV CHD fetuses. There were no associations between anxiety measures and placental features in control fetuses. Conclusions: We report for the first time that elevated prenatal maternal anxiety is associated with altered in vivo placental structures in pregnancies complicated by fetal CHD. Our data suggest that disturbances in placental structure vary based on the type of fetal CHD (SV vs. 2V) in the setting of elevated prenatal maternal anxiety.

scholarly journals KLF2-mediated disruption of PPAR-γ signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow

2018 ◽  
Vol 315 (1) ◽  
pp. H173-H181 ◽  
Author(s):  
Catherine J. Morris ◽  
Rebecca J. Kameny ◽  
Jason Boehme ◽  
Wenhui Gong ◽  
Youping He ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Nadph Oxidase ◽  
Congenital Heart ◽  
Lymph Flow ◽  
Peroxisome Proliferator ◽  
Lymphatic Endothelial Cells ◽  
Ppar Γ

Lymphatic abnormalities associated with congenital heart disease are well described, yet the underlying mechanisms remain poorly understood. Using a clinically relevant ovine model of congenital heart disease with increased pulmonary blood flow, we have previously demonstrated that lymphatic endothelial cells (LECs) exposed in vivo to chronically increased pulmonary lymph flow accumulate ROS and have decreased bioavailable nitric oxide (NO). Peroxisome proliferator-activated receptor-γ (PPAR-γ), which abrogates production of cellular ROS by NADPH oxidase, is inhibited by Krüppel-like factor 2 (KLF2), a flow-induced transcription factor. We hypothesized that chronically increased pulmonary lymph flow induces a KLF2-mediated decrease in PPAR-γ and an accumulation of cellular ROS, contributing to decreased bioavailable NO in LECs. To better understand the mechanisms that transduce the abnormal mechanical forces associated with chronically increased pulmonary lymph flow, LECs were isolated from the efferent vessel of the caudal mediastinal lymph node of control ( n = 5) and shunt ( n = 5) lambs. KLF2 mRNA and protein were significantly increased in shunt compared with control LECs, and PPAR-γ mRNA and protein were significantly decreased. In control LECs exposed to shear forces in vitro, we found similar alterations to KLF2 and PPAR-γ expression. In shunt LECs, NADPH oxidase subunit expression was increased, and bioavailable NO was significantly lower. Transfection of shunt LECs with KLF2 siRNA normalized PPAR-γ, ROS, and bioavailable NO. Conversely, pharmacological inhibition of PPAR-γ in control LECs increased ROS equivalent to levels in shunt LECs at baseline. Taken together, these data suggest that one mechanism by which NO-mediated lymphatic function is disrupted after chronic exposure to increased pulmonary lymph flow is through altered KLF2-dependent PPAR-γ signaling, resulting in increased NADPH oxidase activity, accumulation of ROS, and decreased bioavailable NO. NEW & NOTEWORTHY Lymphatic endothelial cells, when exposed in vivo to chronically elevated pulmonary lymph flow in a model of congenital heart disease with increased pulmonary blood flow, demonstrate Krüppel-like factor 2-dependent disrupted peroxisome proliferator-activated receptor-γ signaling that results in the accumulation of reactive oxygen species and decreased bioavailable nitric oxide.

scholarly journals Congenital Heart Disease–Causing Gata4 Mutation Displays Functional Deficits In Vivo

PLoS Genetics ◽  
2012 ◽  
Vol 8 (5) ◽  
pp. e1002690 ◽  
Author(s):  
Chaitali Misra ◽  
Nita Sachan ◽  
Caryn Rothrock McNally ◽  
Sara N. Koenig ◽  
Haley A. Nichols ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Functional Deficits
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