Atorvastatin Increases Endoglin, SMAD2, Phosphorylated SMAD2/3 and eNOS Expression in ApoE/LDLR Double Knockout Mice
Jazyk angličtina Země Japonsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
19556713
DOI
10.5551/jat.e745
PII: JST.JSTAGE/jat/E745
Knihovny.cz E-zdroje
- MeSH
- anticholesteremika farmakologie MeSH
- aorta chemie MeSH
- apolipoproteiny E genetika MeSH
- ateroskleróza metabolismus MeSH
- atorvastatin MeSH
- cévní endotel chemie MeSH
- endoglin MeSH
- fosforylace MeSH
- imunohistochemie MeSH
- intracelulární signální peptidy a proteiny analýza MeSH
- kyseliny heptylové farmakologie MeSH
- myši knockoutované MeSH
- myši MeSH
- protein Smad2 analýza MeSH
- protein Smad3 analýza MeSH
- pyrroly farmakologie MeSH
- receptory LDL genetika MeSH
- synthasa oxidu dusnatého, typ III analýza MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anticholesteremika MeSH
- apolipoproteiny E MeSH
- atorvastatin MeSH
- endoglin MeSH
- Eng protein, mouse MeSH Prohlížeč
- intracelulární signální peptidy a proteiny MeSH
- kyseliny heptylové MeSH
- protein Smad2 MeSH
- protein Smad3 MeSH
- pyrroly MeSH
- receptory LDL MeSH
- Smad2 protein, mouse MeSH Prohlížeč
- Smad3 protein, mouse MeSH Prohlížeč
- synthasa oxidu dusnatého, typ III MeSH
AIM: Endoglin is a homodimeric transmembrane glycoprotein that has been demonstrated to affect transforming growth factor beta (TGF-beta) signaling and endothelial nitric oxide synthase (eNOS) expression by affecting SMAD proteins in vitro. Thus, in this study we stepped forward to elucidate whether endoglin is co-expressed with SMAD2, phosphorylated SMAD2/3 proteins and eNOS in vivo in atherosclerotic lesions in ApoE/LDLR double knockout mice. In addition, we sought whether endoglin expression as well as the expression of SMAD2, phosphorylated SMAD2/3 and eNOS is affected by atorvastatin treatment. METHODS: Two-month-old female ApoE/LDLR double knockout mice were divided into two groups. The control group was fed with the western type diet whereas in the atorvastatin group, atorvastatin at dose 100 mg/kg per day was added to the same diet. Immunohistochemical and western blot analysis of endoglin, SMAD2, phosphorylated SMAD2/3 and eNOS expressions in aorta were performed. RESULTS: The biochemical analysis showed that administration of atorvastatin significantly decreased level of total cholesterol, VLDL, LDL, TAG, and significantly increased level of HDL cholesterol. Fluorescence immunohistochemistry showed endoglin co-expression with SMAD2, phosphorylated SMAD2/3 and eNOS in aortic endothelium covering atherosclerotic lesions in both control and atorvastatin treated mice. Western blot analysis demonstrated that atorvastatin significantly increased expression of endoglin, SMAD2, phosphorylated SMAD2/3, and eNOS in mice aorta. CONCLUSION: These findings suggest, that endoglin might be interesting marker of endothelial dysfunction and/or atherogenesis which is upregulated by statins implicating potential beneficial role of endoglin and its pathway in atherosclerosis.
Citace poskytuje Crossref.org
