MYOCARDIAL PROTECTION OF HASF IN ACUTE MI

HASF 对急性心肌梗死的心肌保护作用

• 批准号: 8363208
• 负责人: Victor J Dzau
• 金额: $ 0.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363208
• 关键词: Acute; Animals; Apoptosis; Area; Cardiac; Cardiac Myocytes; Chloride Ion; Chlorides; Coronary; Data; Dimensions; EFRAC; Echocardiography; Evans blue stain; Funding; Gadolinium; Grant; Heart; Hour; Hypoxia; Infarction; Ligation; Magnetic Resonance Imaging; Measures; Mesenchymal Stem Cells; Methodology; Methods; Microscopy; Modality; Myocardial; Myosin Heavy Chains; National Center for Research Resources; Pilot Projects; Principal Investigator; Research; Research Infrastructure; Resources; Risk; Scanning; Source; Stem cells; Tetrazolium; Thick; Time; Tissue Harvesting; Transgenic Mice; United States National Institutes of Health; Ventricular Cardiac alpha-Myosin; cost; gadolinium oxide; in vivo; myocardial infarct sizing; novel; overexpression; paracrine; promoter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our lab has recently identified a novel stem cell paracrine factor secreted by mesenchymal stem cells overexpressing Akt that reduces apoptosis of cardiomyocytes exposed to hypoxia. We have generated a heart specific transgenic mouse line to overexpress this factor under the control of the cardiac alpha-myosin heavy chain promoter. The specific aim of proposed study is to assess myocardial infarct size and cardiac function 24 hours post acute coronary ligation using Gadolinium (Gd) hyperconstrast cardiac gated MRI in wild type and alphaMHC-HASF transgenic mice. This would represent a pilot study in which we would compare our current methodologies to MRI to use in long-term, multiple scan (days 14 and 30 post-infarction) assessment of cardiac remodeling in these transgenic mice. Current modalities utilized by our lab to assess myocardial infarct size are dependent on 2,3,5-triphenyl tetrazolium chloride (TTC) and Evan's Blue staining to delineate the area at risk and infarct area. This method requires euthanizing the animals and harvesting tissue. Cardiac function has been assessed by echocardiogram. Gd-hyperconstrast cardiac gated MRI has been shown to be accurate at measuring in vivo infarct size without the need to sacrifice the animal. In addition, cardiac function parameters including ejection fraction (EF), end-diastolic and end-systolic dimensions and volumes, and wall thickness can be evaluated. The major advantage of MRI allows for infarct area and cardiac remodeling parameters to be measured at multiple time-points in the same animal, which reduces the number of animals need and increase the accuracy of data collected.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们的实验室最近发现了一种新的干细胞旁分泌因子，由过表达Akt的间充质干细胞分泌，可减少缺氧条件下心肌细胞的凋亡。 我们已经产生了一个心脏特异性转基因小鼠品系，在心脏α-肌球蛋白重链启动子的控制下过表达该因子。 拟议研究的具体目的是在野生型和alphaMHC-HASF转基因小鼠中使用钆（Gd）高胆固醇心脏门控MRI评估急性冠状动脉结扎后24小时的心肌梗死面积和心脏功能。这将代表一项初步研究，其中我们将比较我们目前的方法与MRI，以用于这些转基因小鼠心脏重塑的长期多次扫描（梗死后14天和30天）评估。 我们实验室目前使用的评估心肌梗死面积的方法依赖于氯化2，3，5-三苯基四氮唑（TTC）和伊文思蓝染色来描绘危险区域和梗死区域。这种方法需要对动物实施安乐死并收获组织。 通过超声心动图评估心脏功能。 已证明Gd-高胆固醇心脏门控MRI在测量体内梗死面积时是准确的，而无需处死动物。此外，还可以评估心脏功能参数，包括射血分数（EF）、舒张末期和收缩末期尺寸和体积以及壁厚。 MRI的主要优点是可以在同一动物的多个时间点测量梗死面积和心脏重塑参数，这减少了所需动物的数量，并提高了收集数据的准确性。