Regulation of Skeletal Muscle Capillary Growth in Exercise and Disease

Capillaries, which are the smallest and most abundant type of blood vessel, form the primary site of gas, nutrient and waste transfer between the vascular and tissue compartments. Skeletal muscle exhibits the capacity to generate new capillaries (angiogenesis) as an adaptation to exercise training, thus ensuring that the heightened metabolic demand of the active muscle is matched by an improved capacity for distribution of gases, nutrients and waste products. This review summarizes the current understanding of the regulation of skeletal muscle capillary growth. The multi-step process of angiogenesis is co-ordinated through the integration of a diverse array of signals associated with hypoxic, metabolic, hemodynamic and mechanical stresses within the active muscle. The contributions of metabolic and mechanical factors to the modulation of key pro- and anti- angiogenic molecules are discussed within the context of responses to a single aerobic exercise bout, short term and long term training. Finally, the paradoxical lack of angiogenesis in peripheral artery disease and diabetes, and the implications for disease progression and muscle health are discussed. Future studies that emphasize an integrated analysis of the mechanisms that control skeletal muscle capillary growth will enable development of targeted exercise programs that effectively promote angiogenesis in healthy individuals and in patient populations.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author