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
-
- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
-
- RERO DOC 327409
- DOI 10.3389/fphys.2019.01003
- Persistent URL
- https://folia.unifr.ch/unifr/documents/308093
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