Cardiovascular disease is the number one cause of death in people over age 65 and 84% of the deaths caused by this affliction occur in the elderly population. Why aging increases the risk of vascular disease is unknown, however age-related decreases in arterial compliance are an independent predictor of cardiovascular risk. Our long-range goal is to delineate the mechanisms by which aging negatively influences vascular structure and function. The objectives of this study are to 1.) Determine the time course and inter- relatedness between changes in aortic morphology and load-induced aortic signaling and 2.) Determine the efficacy of pharmacological intervention in preventing and / or reversing age-associated changes in aortic structure and function. These data will provide important information regarding the causality between age- related changes in vascular structure and function. Our central hypothesis is that aging will be associated with increases in vascular stiffness and a diminished load-induced activation of the mitogen activated protein kinase (MAPK), Akt, and eNOS signaling pathways and that these changes can be attenuated and /or reversed by pharmacological intervention.
The specific aims are: (1) To establish how aging alters aortic compliance, morphology and protein expression, (2) To establish how aging influences mechanically-induced signal transduction in the aorta (3) To establish how glycation end-product cross-link breaker treatment influences age-related aortic compliance and mechanically-induced signal transduction in the aorta, and (4) To expose promising undergraduate students to physiological research. The expected outcomes of this work will: 1.) Determine how aging influences vascular mechanotransduction, 2.) Determine the time course and inter- relatedness of age-associated changes in the vascular material properties, protein expression and signaling, and, 3.) Determine if pharmacological intervention is effective in preventing and/or reversing age-associated vascular dysfunction. Such outcomes will be significant because it is expected to that the new information regarding vascular signaling with aging will provide new targets for preventive and therapeutic interventions that will directly aid in the treatment of age-related cardiovascular disorders. ? ?
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