One of the characteristics of vascular disease, a major cause of morbidity and mortality worldwide, is remodeling of vessel wall structure. These changes in morphology and in protein/lipid/extracellular matrix components in the vessel wall from humans and animal models of disease can be visualized using chromogenic or fluorescent labels and light microscopy. By integrating microscopic with other biochemical or molecular data, important insights can be gained into understanding how the vessel wall is altered during cardiovascular disease. The Microscopy in Medicine (MiM) Core (Core B) will provide centralized facilities and resources for microscopic studies proposed in this Program Project Grant. The MiM Core houses state-of-the- art brightfield/wide field fluorescence microscopes, two laser scanning confocal microscopes, one of which is equipped for live cell imaging, the requisite histology equipment for tissue processing, and image analysis software for extracting quantitative data from the microscope images. In addition to the equipment, the MiM Core staff, Dr. Lula Hilenski, an Assistant Professor in the Department of Medicine and the MiM Core director, and Giji Joseph, the Core histotechnician, provides consultative services for experiment planning and supervision, maintenance, training and support for usage of microscope/histology equipment. Many imaging studies carried out by the PPG project leaders are collaborative efforts with core personnel, reflecting our very active interdisciplinary microscopy users group which spans a range of disciplines, from basic science to clinical and translational research in cardiovascular disease. Because of its centralized location, the MiM Core also functions as a communications center for interactions among these various investigators for data/protocol/reagent sharing.
Blood vessels from experimental animal models or humans with cardiovascular disease exhibit characteristic morphological alterations, including plaque formation, neointimal hypertrophy, lipid and reactive oxygen species accumulation, and inflammatory cell invasion, that can be visualized by microscopic imaging of chromogenic or fluorescent markers on structural or regulatory molecules within vascular tissue/cells, and can be manipulated under a range of experimental conditions. The centralized MiM Core resources provide both intellectual and equipment support for a team of collaborative investigators who, although they study disparate aspects of how oxidative stress and inflammation impact vascular structure, use microscopy as a common experimental tool. These microscopy studies, in conjunction with attendant genetic and molecular data, seek to provide mechanistic insights into chronic disease of the blood vessel wall, a leading cause of illness and death worldwide.
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