Angiotensin II-Derived Reactive Oxygen Species Promote Angiogenesis in Human Late Endothelial Progenitor Cells Through Heme Oxygenase-1 via ERK1/2 and AKT/PI3K Pathways

• Published in: Inflammation Vol. 37; no. 3; pp. 858 - 870
• Main Authors: Mai, Jingting, Qiu, Qiong, Lin, Yong Qing, Luo, Nian Sang, Zhang, Hai Feng, Wen, Zhu Zhi, Wang, Jing Feng, YangXin, Chen
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2014; Springer Nature B.V
• Subjects: Angiotensin II - metabolism; Antioxidants; Apoptosis; Biomedical and Life Sciences; Biomedicine; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Cells, Cultured; Chromones - pharmacology; Endothelial Progenitor Cells - physiology; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; Heme Oxygenase-1 - antagonists & inhibitors; Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - genetics; Humans; Immunology; Internal Medicine; Morpholines - pharmacology; Neovascularization, Physiologic - physiology; Pathology; Pharmacology/Toxicology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Rheumatology; RNA Interference; RNA, Small Interfering; heme oxygenase-1; endothelial progenitor cells; angiotensin II; angiogenesis
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-013-9806-9

Angiotensin II (Ang II), the main component of renin-angiotensin system, could mediate pathogenic angiogenesis in cardiovascular disorders. Late endothelial progenitor cells (EPCs) possess potent self-renewal and angiogenic potency superior to early EPCs, but few study focused on the cross-talk between Ang II and late EPCs. We observed that Ang II could increase reactive oxygen species (ROS) and promote capillary formation in late EPCs. Ang II-derived ROS could also upregulate heme oxygenase-1 (HO-1) expression, and treating late EPCs with HO-1 small interfering RNA or heme oxygenase inhibitor (HO inhibitor) could inhibit Ang II-induced tube formation and increase ROS level and apoptosis rate. In addition, PD98059 and LY294002 pretreatment attenuated Ang II-induced HO-1 expression. Accordingly, Ang II-derived ROS could promote angiogenesis in late EPCs by inducing HO-1 expression via ERK1/2 and AKT/PI3K pathways, and we believe HO-1 might be a promising intervention target in EPCs due to its potent proangiogenic, antioxidant, and antiapoptosis potentials.