Reactive Oxygen Species in Physiologic and Pathologic Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 69

Reactive Oxygen Species in Physiologic
and Pathologic Angiogenesis

Alisa Morss Clyne

Abstract Reactive oxygen species (ROS), including superoxide and hydrogen
peroxide, play a major role in angiogenesis. High ROS doses induce oxidative
stress and subsequent cell death in a variety of cardiovascular diseases, including
hypertension and atherosclerosis. However, low doses of externally applied ROS
directly promote angiogenesis by causing sub-lethal cell membrane damage and
subsequent fibroblast growth factor-2 release, by increasing growth factor pro-
duction, or by enhancing growth factor binding to their receptors. Once angiogenic
growth factor signaling is initiated, ROS are produced intracellularly through
NAD(P)H oxidases and manganese superoxide dismutase as messengers in
downstream growth factor signaling for proliferation, migration, and tube for-
mation. This chapter discusses our current understanding of the vascular ROS
balance in both physiologic and pathologic angiogenesis, as well as innovative
approaches to applying ROS to induce angiogenesis.

1 Overview

Angiogenesis, the growth of new blood vessels from existing vessels, is tightly
controlled by a balance of pro- and anti-angiogenic factors. Pro-angiogenic growth
factors, including vascular endothelial growth factor (VEGF) and fibroblast growth
factor-2 (FGF-2), promote extracellular matrix degradation by cell secreted prote-
ases followed by endothelial cell proliferation, migration, and tube formation [ 1 , 2 ].

A. M. Clyne ( )

Mechanical Engineering and Mechanics, Drexel University,
Philadelphia, PA 19104, USA
e-mail: [e-mail]

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