Reactive Oxygen and Nitrogen Species in Cardiovascular Differentiation of Stem Cells

Abstract

Reactive oxygen species (ROS) and nitric oxide (NO) are involved in a variety of signalling events that regulate physiological and pathophysiological processes in the cardiovascular system. NO also undergoes reactions with oxygen, superoxide ions, and reducing agents to create products that themselves show distinctive reactivity toward particular targets, sometimes with the manifestation of toxic effects, such as nitrosative stress. During early embryogenesis, NADPH oxidases and nitric oxide synthases are already expressed in the growing embryo, suggesting that gradients of ROS and NO may exist in the developing organs and be involved in proper functioning of differentiation programs. During pathophysiological insults of the cardiovascular system, e.g., during hypertension, atherosclerosis, and cardiac infarction, high levels of ROS and NO are generated, thus creating an inflammatory microenvironment which on the one hand contributes to cell damage, apoptosis, and remodeling; but which on the other hand may activate repair processes that involve recruitment and differentiation of stem cells of the cardiovascular cell lineage. In this chapter the current knowledge about activation, recruitment, and differentiation of various cardiovascular stem cell populations by ROS and NO within inflamed tissues and the involved signal transduction cascades is reviewed. Furthermore, the specific microenvironmental requirements for proper stem cell engraftment and maintenance are outlined.