On the possible role of reactive oxygen species in angiogenesis

• Published in: Advances in experimental medicine and biology Vol. 454; p. 295
• Main Authors: Lelkes, P I, Hahn, K L, Sukovich, D A, Karmiol, S, Schmidt, D H
• Format: Journal Article
• Language: English
• Published: United States 1998
• Subjects: Cell Hypoxia - physiology; Cell Respiration; Cells, Cultured; Collagen; Drug Combinations; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Humans; Kinetics; Laminin; Microcirculation - physiology; Neovascularization, Physiologic - physiology; NF-kappa B - metabolism; Oxygen Consumption; Protein Kinase C - metabolism; Proteoglycans; Reactive Oxygen Species - physiology; Skin - blood supply
• ISSN: 0065-2598
• DOI: 10.1007/978-1-4615-4863-8_35

Human microvascular endothelial cells grown on a 3-D reconstituted extracellular matrix (Matrigel) spontaneously and rapidly form a capillary network of tubular structures, thus modeling part of the angiogenic cascade. Exposure of the cells at the time of plating onto Matrigel to a brief episode of hypoxia (40-60) min and subsequent reoxygenation, significantly accelerated (up to 3-fold) the rate of tubular morphogenesis, as determined by computer-aided morphometry. This effect was not dependent on activation of PKC or upregulation/release of angiogenic growth factors. Rather, hypoxia/reoxygenation (H/R), but not hypoxia alone, caused the formation of reactive oxygen species (ROS) and the activation of the nuclear transcription factor NF kappa B, both of which were inhibited by ROS-scavengers, such as pyrollidine dithiocarbamate. Tube formation was inhibited, also under normoxic conditions, by diverse ROS antagonists in a dose-dependent fashion. Our results indicate that angiogenesis is accompanied by and/or requires generation of ROS. We hypothesize that in the clinical setting of hypoxia/reoxygenation during ischemic pre-conditioning, enhanced activation of ROS-dependent intracellular signaling may accelerate the rate of neovascularization also in vivo, thus contributing to the alleviation of certain ischemic lesions.