Atorvastatin-induced endothelial nitric oxide synthase expression in endothelial cells is mediated by endoglin
Language English Country Poland Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26084222
Knihovny.cz E-resources
- MeSH
- Atorvastatin pharmacology MeSH
- Antigens, CD genetics metabolism MeSH
- Endoglin MeSH
- Human Umbilical Vein Endothelial Cells drug effects metabolism MeSH
- Gene Expression MeSH
- Cells, Cultured MeSH
- Humans MeSH
- RNA, Small Interfering genetics MeSH
- Reactive Oxygen Species metabolism MeSH
- Receptors, Cell Surface genetics metabolism MeSH
- Nitric Oxide Synthase Type III metabolism MeSH
- Tumor Necrosis Factor-alpha pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Atorvastatin MeSH
- Antigens, CD MeSH
- Endoglin MeSH
- ENG protein, human MeSH Browser
- RNA, Small Interfering MeSH
- NOS3 protein, human MeSH Browser
- Reactive Oxygen Species MeSH
- Receptors, Cell Surface MeSH
- Nitric Oxide Synthase Type III MeSH
- Tumor Necrosis Factor-alpha MeSH
Endoglin, a transforming growth factor β (TGF-β) receptor type III, is co-expressed with endothelial nitric oxide synthase (eNOS) in aortic endothelium in atherosclerotic plaques of mice. Interestingly, atorvastatin (ATV) is able to increase both endoglin and eNOS expression and reduce plaque size beyond its lipid lowering effects but by unknown mechanisms. We hypothesized whether inflammation modulates ATV-dependent induction of endoglin and eNOS expression in vitro in endothelial cells and whether ATV-induced eNOS expression is regulated via endoglin. After treatment of human umbilical vein endothelial cells (HUVECs) with TNF-α, endoglin and eNOS protein expression was reduced, concomitantly with increased levels of cell surface VCAM-1 and soluble endoglin, as determined by flow cytometry, Western blot and ELISA analyses. By contrast, ATV treatment increased endoglin and eNOS protein expression, while preventing TNF-α-mediated downregulation of endoglin and eNOS protein levels. Moreover, suppression of endoglin using small interfering RNA (siRNA), but not inhibition of TGF-β signaling with SB431542, abrogated ATV-induced eNOS expression. These results suggest that ATV treatment prevents inflammation-reduced endoglin and eNOS expression in endothelial cells and that ATV-induced eNOS expression strongly depends on the proper expression of endoglin in HUVECs. Possible implications of these findings might be reflected in pathological conditions characterized by reduced expression of endoglin and eNOS as for example in hereditary hemorrhagic telangiectasia or in other endothelial dysfunctions.
Kinetics of Biomarkers of Oxidative Stress in Septic Shock: A Pilot Study
