Hypoxia enhances endothelial intercellular adhesion molecule 1 protein level through upregulation of arginase type II and mitochondrial oxidative stress

Liang, Xiujie; Arullampalam, Prakash; Yang, Zhihong; Ming, Xiu-Fen

doi:10.3389/fphys.2019.01003

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Journal article

Hypoxia enhances endothelial intercellular adhesion molecule 1 protein level through upregulation of arginase type II and mitochondrial oxidative stress

Liang, Xiujie Laboratory of Cardiovascular and Aging Research, Medicine Section, Department of Endocrinology, Metabolism, and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Switzerland
Arullampalam, Prakash Laboratory of Cardiovascular and Aging Research, Medicine Section, Department of Endocrinology, Metabolism, and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Switzerland
Yang, Zhihong Laboratory of Cardiovascular and Aging Research, Medicine Section, Department of Endocrinology, Metabolism, and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Switzerland
Ming, Xiu-Fen Laboratory of Cardiovascular and Aging Research, Medicine Section, Department of Endocrinology, Metabolism, and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Switzerland

14.08.2019

Published in:

Frontiers in Physiology. - 2019, vol. 10, p. 1003

English Hypoxia plays a crucial role in the pathogenesis of cardiovascular diseases. Mitochondrial enzyme arginase type II (Arg-II) is reported to lead to endothelial dysfunction and enhance the expression of endothelial inflammatory adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In this study, we investigate the role of Arg-II in hypoxia-induced endothelial activation and the potential underlying mechanisms. Exposure of the human endothelial cells to hypoxia induced a time-dependent increase in Arg-II, HIF1α, HIF2α, and ICAM-1 protein level, whereas no change in the protein level of VCAM-1 and E-selectin was observed. Similar effects were obtained in cells treated with a hypoxia mimetic Dimethyloxaloylglycine (DMOG). Silencing HIF1α, but not HIF2α, reversed hypoxia-induced upregulation of Arg-II. Moreover, silencing Arg-II prevented the ICAM-1 upregulation induced by hypoxia or DMOG. Furthermore, the endothelial cells incubated under hypoxic condition or treated with DMOG or hypoxia enhanced monocyte adhesion, which was inhibited by silencing Arg-II. Lastly, silencing Arg-II prevented hypoxia-induced mitochondrial superoxide production in endothelial cells, and hypoxia-induced ICAM-1 upregulation was reversed by mitochondrial electron transport inhibitor rotenone. These data demonstrate that hypoxia enhances ICAM-1 protein level and monocyte-endothelial interaction through HIF1α-mediated increase in Arg-II protein level on leading to increased mitochondrial reactive oxygen species production. These effects of hypoxia on endothelial cells may play a key role in cardiovascular diseases. Our results suggest that Arg-II could be a promising therapeutic target to prevent hypoxia-induced vascular damage/dysfunction.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language