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.
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