Mouse Cardiac Physiology Core

小鼠心脏生理学核心

基本信息

批准号：
10628913
负责人：
Emily J Tsai
金额：
$ 32.9万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-15 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10628913
关键词：
Acceleration Calcium Channel Calcium Signaling Cardiac Cardiac Myocytes Cardiac health Catheters Chronic Complex Congestive Heart Failure Coronary artery Coupling Disease Echocardiography Equipment Genotype Glean Health Heart Diseases Heart failure Human Human Resources In Vitro Individual Ischemia L-Type Calcium Channels Left Left ventricular structure Ligation Macromolecular Complexes Measurement Measures Microsurgery Mus Myocardial Ischemia Operative Surgical Procedures Pathologic Phenotype Physiologic intraventricular pressure Physiological Physiology Principal Investigator Procedures Program Research Project Grants Regulation Research Personnel Resolution Ryanodine Receptor Calcium Release Channel Signal Transduction Standardization Stress Structure Structure-Activity Relationship Technical Expertise Testing Therapeutic Intervention Time Transgenic Mice Variant Work aorta constriction clinically relevant gene function genetic variant genome resource in vivo innovative technologies insight ischemic injury loss of function macromolecule mouse model multidisciplinary novel therapeutics pressure programs response synergism therapeutic development

Acceleration Calcium Channel Calcium Signaling Cardiac Cardiac Myocytes Cardiac health Catheters Chronic Complex Congestive Heart Failure Coronary artery Coupling Disease Echocardiography Equipment Genotype Glean Health Heart Diseases Heart failure Human Human Resources In Vitro Individual Ischemia L-Type Calcium Channels Left Left ventricular structure Ligation Macromolecular Complexes Measurement Measures Microsurgery Mus Myocardial Ischemia Operative Surgical Procedures Pathologic Phenotype Physiologic intraventricular pressure Physiological Physiology Principal Investigator Procedures Program Research Project Grants Regulation Research Personnel Resolution Ryanodine Receptor Calcium Release Channel Signal Transduction Standardization Stress Structure Structure-Activity Relationship Technical Expertise Testing Therapeutic Intervention Time Transgenic Mice Variant Work aorta constriction clinically relevant gene function genetic variant genome resource in vivo innovative technologies insight ischemic injury loss of function macromolecule mouse model multidisciplinary novel therapeutics pressure programs response synergism therapeutic development

展开

项目摘要

The long-term objective of the Mouse Cardiac Physiology Core is to consolidate the scientific and technical expertise and the specialized equipment necessary to provide: a) standardized, high-quality, and appropriate microsurgery for the induction of chronic heart failure in mice; and b) rigorous, reliable, and accurate in vivo assessment of mouse cardiac physiology. All four projects proposed in this Program Project Grant rely heavily on mouse models of heart failure to test hypotheses about regulatory mechanisms of cardiomyocyte calcium channels in health and cardiac disease. Excitation-contraction coupling, contractility, and cardiac remodeling all require the intricate regulation and coordination of cardiomyocyte calcium channel subunits and their interactomes. Even as investigators focus on studying human loss of function variants, genetically modified mice are indispensable to deciphering the regulatory function of the gene variants. Given that, at times, cardiac genotype-phenotype associations are evidenced only under stress conditions, it will be imperative to examine cardiac structure and function of transgenic mice under baseline conditions and following chronic cardiac stress. As such, the Mouse Cardiac Physiology Core will address three specific aims: 1. Performing survival microsurgeries on mice to induce either chronic pressure-overload or chronic ischemic stress upon the left ventricle. This will be accomplished through transverse aortic constriction and left coronary artery ligation, respectively. 2. Assessing in vivo cardiac structure and function of experimental mice over time via serial echocardiograms. 3. Determining the left ventricular pressure-volume relationship using in vivo invasive conductance catheter measurements. By streamlining these essential procedures and analyses, the Mouse Cardiac Physiology Core will accelerate the pace at which our Investigators obtain invaluable insights into the structure and function of calcium channel complexes in cardiac physiology and disease. Thus ,our work in the Mouse Cardiac Physiology Core will be synergistic with that of the four individual program projects and the Human Phenotyping Core. We expect that our cumulative findings will identify clinically relevant regulatory mechanisms and structure-function relationships that can then facilitate novel therapeutic developments and interventions.

小鼠心脏生理核心的长期目标是巩固科学和技术专业知识和提供的专业设备：a）标准化，高质量且合适的设备小鼠慢性心力衰竭的显微外科手术； b）体内严格，可靠和准确评估小鼠心脏生理。该计划项目赠款中提出的所有四个项目都严重依赖关于心脏失效的小鼠模型，以测试有关心肌细胞钙调节机制的假设健康和心脏病的渠道。激发诱导耦合，收缩力和心脏重塑所有这些都需要对心肌细胞钙通道亚基的复杂调节和协调相互作用。即使研究人员专注于研究人类功能变异的丧失，基因修改了小鼠是必不可少的，即破译基因变体的调节功能。鉴于这有时是心脏基因型 - 表型关联仅在应力条件下才能证明基线条件下转基因小鼠的心脏结构和功能，并遵循慢性心脏压力。因此，小鼠心脏生理核心将解决三个具体目标： 1。在小鼠上执行生存显微镜以诱导慢性压力超负荷或慢性左心室的缺血压力。这将通过横向主动脉收缩来完成并分别左冠状动脉结扎。 2。随着时间的流逝，评估实验小鼠的体内心脏结构和功能超声心动图。 3。使用体内侵入性电导来确定左心室压力量的关系导管测量。通过简化这些基本过程和分析，小鼠心脏生理核心将加速我们的研究人员获得对钙通道的结构和功能的宝贵见解的速度心脏生理和疾病中的复合物。因此，我们在小鼠心脏生理核心的工作将是与四个单独的计划项目和人类表型核心的核心协同作用。我们期望这一点我们的累积发现将确定临床相关的调节机制和结构功能然后可以促进新的治疗发展和干预措施的关系。