Atorvastatin-induced endothelial nitric oxide synthase expression in endothelial cells is mediated by endoglin
Jazyk angličtina Země Polsko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26084222
Knihovny.cz E-zdroje
- MeSH
- atorvastatin farmakologie MeSH
- CD antigeny genetika metabolismus MeSH
- endoglin MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků metabolismus MeSH
- exprese genu MeSH
- kultivované buňky MeSH
- lidé MeSH
- malá interferující RNA genetika MeSH
- reaktivní formy kyslíku metabolismus MeSH
- receptory buněčného povrchu genetika metabolismus MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- TNF-alfa farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- atorvastatin MeSH
- CD antigeny MeSH
- endoglin MeSH
- ENG protein, human MeSH Prohlížeč
- malá interferující RNA MeSH
- NOS3 protein, human MeSH Prohlížeč
- reaktivní formy kyslíku MeSH
- receptory buněčného povrchu MeSH
- synthasa oxidu dusnatého, typ III MeSH
- TNF-alfa 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.
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