Use of echocardiography for the phenotypic assessment of genetically altered mice

2003 ◽  
Vol 13 (3) ◽  
pp. 227-239 ◽  
Author(s):  
Keith A. Collins ◽  
Claudia E. Korcarz ◽  
Roberto M. Lang
Keyword(s):  
Molecular Mechanisms ◽  
Cardiac Development ◽  
Contrast Echocardiography ◽  
Left Ventricular ◽  
Mouse Heart ◽  
Endocardial Border ◽  
Heart Beating ◽  
Cardiac Evaluation ◽  
Endocardial Border Delineation ◽  
And Function

Transgenic mice displaying abnormalities in cardiac development and function represent a powerful new tool for understanding molecular mechanisms underlying normal cardiovascular function and the pathophysiological bases of human cardiovascular disease. Complete cardiac evaluation of phenotypic changes in mice requires the ability to noninvasively assess cardiovascular structure and function in a serial manner. However, the small mouse heart beating at rates in excess of 500 beats/min presents unique methodological challenges. Two-dimensional and Doppler echocardiography have been recently used as effective, noninvasive tools for murine imaging, because quality images of cardiac structures and valvular flows can be obtained with newer high-frequency transthoracic transducers. We will discuss the use of echocardiography for the assessment of 1) left ventricular (LV) chamber dimensions and wall thicknesses, 2) LV mass, 3) improved endocardial border delineation using contrast echocardiography, 4) LV contractility using ejection phase indices and load-independent indices, 5) vascular properties, and 6) LV diastolic performance. Evaluation of cardiovascular performance in closed chest mice is feasible in a variety of murine models using Doppler echocardiographic imaging.

Abstract 96: Inactivation of Neddylation Causes Left Ventricular Noncompaction Cardiomyopathy Through Suppressing YAP Signaling

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Jianqiu Zou ◽  
Wenxia Ma ◽  
Jie Li ◽  
Rodney Littlejohn ◽  
Il-man Kim ◽  
...  
Keyword(s):  
Cardiac Development ◽  
Heart Diseases ◽  
Left Ventricular ◽  
Late Gestation ◽  
Mouse Heart ◽  
Cardiomyocyte Proliferation ◽  
Transcription Cofactor ◽  
Wild Type Counterpart

Rationale: Cardiac development is orchestrated by a number of growth factors, transcription factors and epigenetic regulators, perturbation of which can lead to congenital heart diseases and cardiomyopathies. However, the role of novel ubiquitin-like protein modifiers, such as NEDD8 (neural precursor cells expressed developmentally downregulated 8), in cardiac development is unknown. Objectives: The objective of this study was to determine the significance of NEDD8 modification (neddylation) during perinatal cardiac development. Methods and Results: Neddylated proteins and NEDD8 enzymes were highly abundant in fetal and neonatal hearts but downregulated in adult hearts. We employed an αMHC Cre transgene to delete NAE1, a subunit of the NEDD8 E1 enzyme, in the perinatal mouse heart. Cardiac-specific deletion of NAE1 (NAE1 CKO ) significantly decreased neddylated proteins in the heart. The NAE1 CKO mice displayed cardiac hypoplasia, ventricular non-compaction and heart failure during late gestation, which became more pronounced by postnatal day 1 and led to perinatal lethality. Mechanistically, genetic deletion or pharmacological inhibition of NAE1 resulted in accumulation of Hippo kinases Mst1 and LATS1/2, which in turn phosphorylated and inactivated YAP, a transcription cofactor necessary for cardiomyocyte proliferation, leading to dysregulation of a number of cell cycle-regulatory genes and blockade of cardiomyocyte proliferation in vivo and in vitro . Reactivation of YAP signaling by overexpression of a constitutively-active YAP mutant (YAP 5SA ), but not its wild-type counterpart, overcame the blockade of cardiomyocyte proliferation induced by inhibition of NAE1. Conclusions: Our findings establish the importance of neddylation in the heart, more specifically, in ventricular chamber maturation, and identify neddylation as a novel regulator of Hippo-YAP signaling to promote cardiomyocyte proliferation.

scholarly journals Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent

1998 ◽  
Vol 32 (3) ◽  
pp. 746-752 ◽  
Author(s):  
Jerald L Cohen ◽  
Jorge Cheirif ◽  
Douglas S Segar ◽  
Linda D Gillam ◽  
John S Gottdiener ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Left Ventricular ◽  
Endocardial Border ◽  
Endocardial Border Delineation

scholarly journals Atrial Electrophysiological Remodeling and Fibrillation in Heart Failure

2016 ◽  
Vol 10s1 ◽  
pp. CMC.S39713 ◽  
Author(s):  
Sandeep V. Pandit ◽  
Antony J. Workman
Keyword(s):  
Heart Failure ◽  
Molecular Mechanisms ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Ion Currents ◽  
Multiple Variables ◽  
The Individual ◽  
And Function

Heart failure (HF) causes complex, chronic changes in atrial structure and function, which can cause substantial electrophysiological remodeling and predispose the individual to atrial fibrillation (AF). Pharmacological treatments for preventing AF in patients with HF are limited. Improved understanding of the atrial electrical and ionic/molecular mechanisms that promote AF in these patients could lead to the identification of novel therapeutic targets. Animal models of HF have identified numerous changes in atrial ion currents, intracellular calcium handling, action potential waveform and conduction, as well as expression and signaling of associated proteins. These studies have shown that the pattern of electrophysiological remodeling likely depends on the duration of HF, the underlying cardiac pathology, and the species studied. In atrial myocytes and tissues obtained from patients with HF or left ventricular systolic dysfunction, the data on changes in ion currents and action potentials are largely equivocal, probably owing mainly to difficulties in controlling for the confounding influences of multiple variables, such as patient's age, sex, disease history, and drug treatments, as well as the technical challenges in obtaining such data. In this review, we provide a summary and comparison of the main animal and human electrophysiological studies to date, with the aim of highlighting the consistencies in some of the remodeling patterns, as well as identifying areas of contention and gaps in the knowledge, which warrant further investigation.

Usefulness of harmonic imaging for left ventricular opacification and endocardial border delineation by optison

2000 ◽  
Vol 85 (6) ◽  
pp. 795-799 ◽  
Author(s):  
Hend A Al-Mansour ◽  
Sharon L Mulvagh ◽  
Geralyn M Pumper ◽  
Kyle W Klarich ◽  
David A Foley
Keyword(s):  
Left Ventricular ◽  
Harmonic Imaging ◽  
Endocardial Border ◽  
Endocardial Border Delineation

Left ventricular volumes and function in the embryonic mouse heart

1997 ◽  
Vol 273 (3) ◽  
pp. H1368-H1376 ◽  
Author(s):  
N. Tanaka ◽  
L. Mao ◽  
F. A. DeLano ◽  
E. M. Sentianin ◽  
K. R. Chien ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Fluorescent Imaging ◽  
Left Ventricular Volumes ◽  
Mouse Heart ◽  
Embryonic Mouse ◽  
End Diastolic Volume ◽  
Or Gene ◽  
The Individual ◽  
And Function

This study describes miniaturized technology for the in vivo analysis of the volume and function of the embryonic mouse heart and the application of this technology to study the normal embryonic left ventricle (LV) at two stages of development. With the use of microsurgical techniques, embryos from embryonic day (ED) 10.5 (ED10.5) to ED16 were delivered individually from litters of normal dams, and cardiac visualization was achieved with the use of intravital microscopy by transillumination, with the umbilical circulation intact. At ED10.5-11, the heart could be imaged in color in the intact embryo, whereas at ED12.5 it was necessary to open the chest; at ED13.5-14.5, fluorescent imaging with the use of microinjection of fluorescein-conjugated albumin was necessary to visualize the LV chamber. At ED10.5-11, the LV end-diastolic volumes averaged 0.16 microliter (n = 14), and at ED13.5-14.5, they averaged 0.57 microliter (n = 16). At both ages there was a positive linear relationship between the LV end-diastolic volume and the stroke volume despite substantial variations in individual heart rates, reflecting the relative uniformity of the LV ejection fractions within each age group. The average of the individual ejection fractions was 27.4% at ED10.5-11 and 58.4% at ED13.5-14.5, the latter being within the normal range for the adult rodent heart. These methods will be useful for assessing in vivo cardiac function at ED10.5 and older murine embryos in litters of transgenic or gene-targeted mice when the mutation leads to later embryonic lethality.

Enhanced Left Ventricular Endocardial Border Delineation with an Intravenous Injection of SonoVue, a New Echocardiography Contrast Agent:.

2000 ◽  
Vol 17 (8) ◽  
pp. 705-711 ◽  
Author(s):  
Roxy Senior ◽  
Antoinette Kenny ◽  
Ove Andersson ◽  
Kenneth Caidahl ◽  
Per Carlens ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Intravenous Injection ◽  
Left Ventricular ◽  
Endocardial Border ◽  
Endocardial Border Delineation

Assessment of Coronary Microcirculation with Myocardial Contrast Echocardiography

2018 ◽  
Vol 24 (25) ◽  
pp. 2943-2949 ◽  
Author(s):  
Trifunovic Danijela ◽  
Dudic Jelena ◽  
Petrovic Olga ◽  
Vasiljevic-Pokrajcic Zorana
Keyword(s):  
Contrast Echocardiography ◽  
Left Ventricular ◽  
Coronary Microcirculation ◽  
Myocardial Contrast Echocardiography ◽  
Special Focus ◽  
Endocardial Border ◽  
Non Invasive ◽  
Perfusion Studies ◽  
Reliable Assessment ◽  
Wall Motion Abnormalities

Myocardial contrast echocardiography has been used in clinical arena and for scientific research extensively in the last fifteen years. This non-invasive, bed-side and radiation free imaging technique offers several important possibilities: better delineation of the endocardial border, more reliable assessment of the left ventricular wall motion abnormalities, both in rest and during stress, and myocardial perfusion evaluation. Here we provide an overview on different applications of the myocardial contrast echocardiography in the ischemic heart disease with the special focus on perfusion studies and evaluation of coronary microcirculation.

scholarly journals HIF-1α is required for development of the sympathetic nervous system

2019 ◽  
Vol 116 (27) ◽  
pp. 13414-13423 ◽  
Author(s):  
Romana Bohuslavova ◽  
Radka Cerychova ◽  
Frantisek Papousek ◽  
Veronika Olejnickova ◽  
Martin Bartos ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Molecular Mechanisms ◽  
Cardiac Development ◽  
Sympathetic Innervation ◽  
Cardiac Contractility ◽  
Hypoxia Inducible Factor ◽  
Left Ventricular ◽  
Conditional Knockout ◽  
Sympathetic Nervous

The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the Hif1a gene encoding the transcription factor hypoxia-inducible factor 1α (HIF-1α) is mediated by an Islet1-Cre transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These Hif1aCKO mice demonstrate significantly decreased perinatal survival and impaired left ventricular function. The absence of HIF-1α impaired the survival and proliferation of preganglionic and postganglionic neurons of the sympathetic system, respectively. These defects resulted in hypoplasia of the sympathetic ganglion chain and decreased sympathetic innervation of the Hif1aCKO heart, which was associated with decreased cardiac contractility. The number of chromaffin cells in the adrenal medulla was also decreased, indicating a broad dependence on HIF-1α for development of the sympathetic nervous system.

scholarly journals MicroRNA Clusters in the Adult Mouse Heart: Age-Associated Changes

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaomin Zhang ◽  
Gohar Azhar ◽  
Emmanuel D. Williams ◽  
Steven C. Rogers ◽  
Jeanne Y. Wei
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Cardiac Development ◽  
Mouse Heart ◽  
Substantial Impact ◽  
Genomic Location ◽  
Microrna Cluster ◽  
Protein Components ◽  
And Function ◽  
Cytoskeleton Dynamics

The microRNAs and microRNA clusters have been implicated in normal cardiac development and also disease, including cardiac hypertrophy, cardiomyopathy, heart failure, and arrhythmias. Since a microRNA cluster has from two to dozens of microRNAs, the expression of a microRNA cluster could have a substantial impact on its target genes. In the present study, the configuration and distribution of microRNA clusters in the mouse genome were examined at various inter-microRNA distances. Three important microRNA clusters that are significantly impacted during adult cardiac aging, the miR-17-92, miR-106a-363, and miR-106b-25, were also examined in terms of their genomic location, RNA transcript character, sequence homology, and their relationship with the corresponding microRNA families. Multiple microRNAs derived from the three clusters potentially target various protein components of the cdc42-SRF signaling pathway, which regulates cytoskeleton dynamics associated with cardiac structure and function. The data indicate that aging impacted the expression of both guide and passenger strands of the microRNA clusters; nutrient stress also affected the expression of the three microRNA clusters. The miR-17-92, miR-106a-363, and miR-106b-25 clusters are likely to impact the Cdc42-SRF signaling pathway and thereby affect cardiac morphology and function during pathological conditions and the aging process.

Sign in / Sign up

Export Citation Format

Share Document