CARDIOVASCULAR PHENOTYPING IN MICE

描述(由申请人提供)： 该奖项将为建立和运营小鼠心血管表型鉴定的核心设施提供支持。它还将支持三个对衰老研究有意义的项目：1)成年小鼠心肌病；2)年龄引起的小鼠胎盘功能不全；以及3)功能性肿瘤血管生成拟态。该申请包括指导选择转化性心血管研究职业的年轻研究人员的具体计划。特定的长期职业目标：1)操作国际公认的心血管疾病小鼠表型鉴定核心设施；2)促进对可遗传扩张型心肌病细胞基础的了解，开发具有临床应用潜力的诊断和治疗方法；3)确定小鼠疾病状态下母体-胎盘循环受损的性质和程度，概括重要的临床情况，并开发有可能临床应用的治疗策略；4)应用有关肿瘤血管生成拟态通道功能的新发现知识，以改进癌症的诊断和治疗；以及5)开发和实施翻译小鼠心血管研究方面的培训计划，致力于促进未来独立研究人员的职业生涯。这些目标将通过应用现有方法和开发新的方法在体内研究小鼠心血管功能来实现。该项目最初将依靠超声波检查和心导管检查来实现其特定目标。在获奖过程中，将测试和实施小鼠心血管研究的新方法。最终，在小鼠身上进行的这些研究获得的信息将为开发心血管疾病患者诊断和治疗方面的新的和可行的进展奠定基础。

DESCRIPTION (provided by applicant): This Award will provide support for the establishment and operation of a core facility for mouse cardiovascular phenotyping. It will also support three projects with implications for aging research: 1) adult-onset cardiomyopathy in mice; 2) age-induced placental insufficiency in mice; and 3) functional tumor vasculogenic mimicry. The application includes specific plans to mentor young investigators who select careers in translational cardiovascular research. Specific long-term career goals: 1) Operate an internationally recognized cardiovascular mouse phenotyping core facility; 2) advance the understanding of the cellular basis of heritable dilated cardiomyopathy, and develop diagnostic and therapeutic modalities with the potential for clinical application; 3) determine the nature and magnitude of impairment of maternal-placental circulation in murine disease states which recapitulate important clinical conditions, and develop therapeutic strategies which have potential for clinical application; 4) apply newfound knowledge about the function of tumor vasculogenic mimicry channels toward improved cancer diagnosis and treatment; and 5) develop and implement a training program in translational mouse cardiovascular research, dedicated toward fostering the careers of future independent investigators. These goals will be pursued by application of current methods and development of new methods for investigation of mouse cardiovascular function in vivo. The project will initially rely on ultrasonography and cardiac catheterization to achieve its Specific Aims. During the course of the Award, new methods for cardiovascular studies in mice will be tested and implemented. Ultimately, the information gained by these studies in mice will form the foundation for the development of novel and feasible advances in the diagnosis and treatment of patients with cardiovascular disorders.