Abdominal aortic aneurysm disease is a common and lethal health problem of older Americans. Substantial evidence links sedentary existence and resulting pro-inflammatory aortic conditions to the pathogenesis of AAA disease. Insights derived from investigations in animal models and high risk patient groups and care of AAA patients have help define our LONG TERM OBJECTIVE;to identify, validate and apply effective nonsurgical therapies to the treatment of AAA disease. The purpose of this proposal is to test the ability of lower extremity exercise to reduce AAA risk, limit small aneurysm progression and modify biologic markers of disease. We have two SPECIFIC AIMS: First, we will perform a cross-sectional correlation study to determine whether lifetime physical activity and measured exercise capacity represent independent risk factors for AAA disease. These studies will test our hypothesis that aortic diameter and activity level will be independently and inversely related;that is, abdominal aorta size adjusted for age, will be increased in A) inidividuals completing questionnaires indicating persistently low levels of physical activity or B) have reduced exercise capacity as defined by clinical testing. Second, we will perform a prospective, randomized controlled longitudinal trial of exercise to suppress small AAA progression. The impact of training will be monitored by both serial surveillance ultrasound imaging and surrogage biologic markers and imaging of disease progression. This will test our hypothesis that supervised exercise training will reduce AAA expansion rates and/or diminish surrogate markers of disease progression. To ACHIEVE THESE AIMS we will apply analyze life time physical activity to several hundred patients with the new diagnosis of small AAA disease, measure aortic diameter in a large cohort of patients with previously defined exercise capacity, and apply supervised exercise training to an additional cohort of small aneurysm patients. This application is RELEVANT to public health in that we will test a new and low risk method of preventing the development or progression of AAA disease, a potentially life threatening condition. In addition, we will develop a framework to test, measure and compare the effectiveness of future novel therapies.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
United States
Zip Code
Pan, Cuiping; McInnes, Gregory; Deflaux, Nicole et al. (2017) Cloud-based interactive analytics for terabytes of genomic variants data. Bioinformatics 33:3709-3715
Kitagawa, Toshiro; Kosuge, Hisanori; Uchida, Masaki et al. (2017) RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm. J Magn Reson Imaging 45:1144-1153
Suh, Ga-Young; Choi, Gilwoo; Herfkens, Robert J et al. (2016) Three-Dimensional Modeling Analysis of Visceral Arteries and Kidneys during Respiration. Ann Vasc Surg 34:250-60
Betz, Heather Hayes; Myers, Jonathan; Jaffe, Alyssa et al. (2015) Reproducibility of the Veterans Physical Activity Questionnaire in an elderly population. J Phys Act Health 12:376-81
Nakayama, Karina H; Joshi, Prajakta A; Lai, Edwina S et al. (2015) Bilayered vascular graft derived from human induced pluripotent stem cells with biomimetic structure and function. Regen Med 10:745-55
Arzani, Amirhossein; Les, Andrea S; Dalman, Ronald L et al. (2014) Effect of exercise on patient specific abdominal aortic aneurysm flow topology and mixing. Int J Numer Method Biomed Eng 30:280-95
Maegdefessel, Lars; Azuma, Junya; Tsao, Philip S (2014) MicroRNA-29b regulation of abdominal aortic aneurysm development. Trends Cardiovasc Med 24:1-6
Spin, Joshua M; Tsao, Philip S (2014) Battle of the bulge: miR-195 versus miR-29b in aortic aneurysm. Circ Res 115:812-3
Arzani, Amirhossein; Suh, Ga-Young; Dalman, Ronald L et al. (2014) A longitudinal comparison of hemodynamics and intraluminal thrombus deposition in abdominal aortic aneurysms. Am J Physiol Heart Circ Physiol 307:H1786-95
Maegdefessel, Lars; Dalman, Ronald L; Tsao, Philip S (2014) Pathogenesis of abdominal aortic aneurysms: microRNAs, proteases, genetic associations. Annu Rev Med 65:49-62

Showing the most recent 10 out of 50 publications