25-Hydroxycholesterol impairs endothelial function and vasodilation by uncoupling and inhibiting endothelial nitric oxide synthase
| Autor: | Jing Chen, Ze-Bang Lin, Dan-Hong Su, Zhi-Jun Ou, Zhi-Ping Wang, Jing-Song Ou, Yan Li, Tian-Pu Cheng, Jun Tao, Wei-Ping Dai, Yin-Ke Yang, Tian-Tian Wang, Xiang Liu, Ying-Ying Wu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Nitric Oxide Synthase Type III Physiology Endocrinology Diabetes and Metabolism Apoptosis 030204 cardiovascular system & hematology In Vitro Techniques Nitric Oxide Nitric oxide Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enos Cell Movement Superoxides Physiology (medical) Internal medicine Heat shock protein medicine Animals Endothelium Endothelial dysfunction Enzyme Inhibitors Protein kinase B Cell Proliferation Tube formation biology Superoxide Uncoupling Agents Endothelial Cells medicine.disease biology.organism_classification Hydroxycholesterols Rats Endothelial stem cell Vasodilation 030104 developmental biology Endocrinology chemistry Cattle sense organs Inflammation Mediators |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 311(4) |
| ISSN: | 1522-1555 |
| Popis: | Endothelial dysfunction is a key early step in atherosclerosis. 25-Hydroxycholesterol (25-OHC) is found in atherosclerotic lesions. However, whether 25-OHC promotes atherosclerosis is unclear. Here, we hypothesized that 25-OHC, a proinflammatory lipid, can impair endothelial function, which may play an important role in atherosclerosis. Bovine aortic endothelial cells were incubated with 25-OHC. Endothelial cell proliferation, migration, and tube formation were measured. Nitric oxide (NO) production and superoxide anion generation were determined. The expression and phosphorylation of endothelial NO synthase (eNOS) and Akt as well as the association of eNOS and heat shock protein (HSP)90 were detected by immunoblot analysis and immunoprecipitation. Endothelial cell apoptosis was monitored by TUNEL staining and caspase-3 activity, and expression of Bcl-2, Bax, cleaved caspase-9, and cleaved caspase-3 were detected by immunoblot analysis. Finally, aortic rings from Sprague-Dawley rats were isolated and treated with 25-OHC, and endothelium-dependent vasodilation was evaluated. 25-OHC significantly inhibited endothelial cell proliferation, migration, and tube formation. 25-OHC markedly decreased NO production and increased superoxide anion generation. 25-OHC reduced the phosphorylation of Akt and eNOS and the association of eNOS and HSP90. 25-OHC also enhanced endothelial cell apoptosis by decreasing Bcl-2 expression and increasing cleaved caspase-9 and cleaved caspase-3 expressions as well as caspase-3 activity. 25-OHC impaired endothelium-dependent vasodilation. These data demonstrated that 25-OHC could impair endothelial function by uncoupling and inhibiting eNOS activity as well as by inducing endothelial cell apoptosis. Our findings indicate that 25-OHC may play an important role in regulating atherosclerosis. |
| Databáze: | OpenAIRE |
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