ANGIOGENESIS AND THE MECHANISMS OF EXERCISE TRAINING IN PAD

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Peripheral arterial disease (PAD) impairs arterial blood flow to the legs and is a major indicator of systemic atherosclerosis. Approximately 1/3 of patients with PAD have claudication, defined as pain in one or both legs during walking, that is relieved by rest. Patients with claudication have a marked impairment in exercise performance. Goals of treatment for PAD patients include risk-factor modification and antiplatelet drug therapy to address increased cardiovascular mortality risk. Supervised exercise training is the most efficacious treatment to improve walking capacity, demonstrated in many randomized trials. Neither the physiology of claudication nor the mechanisms by which exercise training improves walking in people with claudication are understood and therefore there is an urgent need for clinical research directed towards defining the basis of the exercise training changes induced in PAD patients. In this stud7, men and women over 40 years, with claudication and an ABI of < .90 at rest will be recruited from Duke University Medical Center and the University of Colorado Health Sciences Center. Patients will be randomized to a supervised or home-based exercise program. Evaluations will be at baseline, 3 weeks (for the supervised exercisers), and at 3 months. Age-gender matched healthy controls will be tested at baseline. The central hypothesis is that the beneficial effects of exercise training are primarily mediated through an angiogenic effect, or the formation of new blood vessels.