CELLULAR AND MOLEC STUDIES OF ABDOMINAL AORTIC ANEURYSM

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In response to Research Objective #4 of the NIA Pilot Research Grant Program, this application addresses the cellular and molecular mechanisms of cardiovascular aging. Abdominal aortic aneurysm (AA) is a deadly disease characterized by dilatation, weakening, and sudden rupture of the lower portion of the largest elastic artery-the aorta. AAA is a disease of aging men, with peak incidence past the age of 60. Basic and clinical studies support the idea that AA is caused by age-related, structural weakening of the aortic wall's amine oxidase (SSAO) indicate that in weanling rats, inhibition of the enzyme results in morphologic changes in elastin and patho-physiology mimicking known aging changes that lead to AAA in humans. To fully develop this model of AAA, and obtain preliminary data that will begin to define the mechanisms underlying development of AAA in older individuals, we propose these pilot experiments. 1) a time-course experiment that will define aortic structural and physiological changes occurring in the model; we will compare these changes to those found in aging aorta and then do: 2) a differential gene display experiment to define important changes in gene expression that accompany early AAA development in this model. These studies will focus on one important aspect of vascular aging, i.e., degenerative elastin changes in the aorta. By developing this animal model, and focusing on genetic changes that accompany aortic aging and the development of AAA, we will be in a position to pursue a more complex mechanistic future project addressing this important vascular disease of aging.