Exercise stimulates angiogenesis in skeletal muscle. The increased capillarity improves muscle function and quality of life in patients with peripheral arterial insufficiency (PAI). Thus, either exercise training or proangiogenic drug therapies (if exercise is contraindicated) could be helpful to these patients. However, the growth factors, receptors, and signaling pathways involved in skeletal muscle angiogenesis are not well characterized. Therefore, these studies will address three Specific Aims: 1) to characterize the time course of alterations in the content and expression of angiogenic growth factors in red and white gastrocnemius muscle of both normal rats and rats with hindlimb ischemia during an exercise training program; 2) to characterize the time course of alterations in the content and expression of receptors for angiogenic growth factors in red and white gastrocnemius muscle of both normal rats and rats with hindlimb ischemia during an exercise training program; and 3) to determine whether a functioning nitric oxide signaling pathway or the angiopoietin/Tie-2 system is essential for exercise- stimulated angiogenesis. These studies will utilize femorally- ligated rats, a model of PAI. Rats will follow a treadmill exercise program known to stimulate angiogenesis.
For Specific Aims 1 and 2, levels of growth factors (VEGF, bFGF, angiopoietin- 1, and angiopoietin-2) and their receptors will be assessed over the initial period of vascular expansion (28 d) and correlated with capillary growth.
For Specific Aim 3, the effect of nitric oxide synthase or Tie-2 (angiopoietin receptor) inhibition on capillary growth and cell proliferation will be evaluated following approximately 2 w of exercise. These studies will advance understanding of skeletal muscle angiogenesis and may suggest treatments for patients with PAI.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL010406-02
Application #
6402741
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (02))
Program Officer
Schucker, Beth
Project Start
2001-07-01
Project End
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
University of Missouri-Columbia
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Haas, Tara L; Lloyd, Pamela G; Yang, Hsiao-Tung et al. (2012) Exercise training and peripheral arterial disease. Compr Physiol 2:2933-3017
Lloyd, Pamela G; Prior, Barry M; Yang, Hsiao T et al. (2003) Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. Am J Physiol Heart Circ Physiol 284:H1668-78
Lloyd, P G; Yang, H T; Terjung, R L (2001) Arteriogenesis and angiogenesis in rat ischemic hindlimb: role of nitric oxide. Am J Physiol Heart Circ Physiol 281:H2528-38