Abstract

The role of capillaries is to serve as the interface for delivery of oxygen and removal of metabolites to/from tissues. During the past decade there has been a proliferation of studies that have advanced our understanding of angiogenesis, demonstrating that tissue capillary supply is under strict control during health but poorly controlled in disease, resulting in either excessive capillary growth (pathological angiogenesis) or losses in capillarity (rarefaction). Given that skeletal muscle comprises nearly 40% of body mass in humans, skeletal muscle capillary density has a significant impact on metabolism, endocrine function, and locomotion and is tightly regulated at many different levels. Skeletal muscle is also high adaptable and thus one of the few organ systems that can be experimentally manipulated (e.g., by exercise) to study physiological regulation of angiogenesis. This review will focus on the methodological concerns that have arisen in determining skeletal muscle capillarity and highlight the concepts that are reshaping our understanding of the angio-adaptation process. We also summarize selected new findings (physical influences, molecular changes, and ultrastructural rearrangement of capillaries) that identify areas of future research with the greatest potential to expand our understanding of how angiogenesis is normally regulated, and that may also help to better understand conditions of uncontrolled (pathological) angiogenesis.

Highlights

  • There is wide recognition [17, 38, 126] and a surfeit of epidemiologic evidence that links the benefits of exercise training with a decreased risk of cardiovascular diseases

  • Studies aimed at understanding angioadaptation and regulation of angiogenesis in muscle provide a great opportunity to investigate and understand the complexity and highly structured choreography essential for controlled regulation of angiogenesis

  • Given the number of diseases that involve aberrant regulation of angiogenesis, resulting in either uncontrolled vessel growth or capillary rarefaction, it is imperative that a fundamental understanding of the mechanisms that work to effectively control angiogenesis is attained, before we can truly fully understand pathological dysregulation

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Summary

Introduction

There is wide recognition [17, 38, 126] and a surfeit of epidemiologic evidence that links the benefits of exercise training with a decreased risk of cardiovascular diseases. H327 of the angiogenic processes, demonstrating that capillary growth in skeletal muscle is a process that is tightly regulated at many different levels [see reviews [29, 59, 101]]. This regulation follows the principles of a control circuit. We will use an integrative review to assess the impact of, and responses to, altered muscle activity and summarize selected new findings that identify areas of future research with the greatest potential to expand our understanding of the regulation of skeletal muscle angiogenesis and improve therapeutic efficacy

Methodology
Summary and Relevance
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