Reactive oxygen species as signaling molecules in cardiovascular differentiation of embryonic stem cells and tumor-induced angiogenesis.

Besides the well known pathophysiological impact of oxidative stress in cardiovascular disease, reactive oxygen species (ROS) generated at low concentrations exert a role as signaling molecules that are involved in signal transduction cascades of numerous growth factor-, cytokine-, and hormone-mediated pathways, and regulate biological effects such as apoptosis, cell proliferation, and differentiation. Embryonic stem cells have the capacity to differentiate into the cardiovascular cell lineage. Furthermore, upon confrontation culture with tumor tissue, they form blood vessel-like structures that induce tumor-induced angiogenesis within tumor tissues. The role of ROS in cardiovascular differentiation of embryonic stem cells appears to be antagonistic. Whereas continuous exposure to ROS results in inhibition of cardiomyogenesis and vasculogenesis, pulse chase exposure to low-level ROS enhances differentiation toward the cardiomyogenic as well as vascular cell lineage. This review summarizes the current knowledge of ROS-induced cardiovascular differentiation of embryonic stem cells as well as the role of ROS in tumor-induced angiogenesis. Antioxid. Redox Signal. 7, 1423-1434.