21440631 OR Endoglin as a possible marker of atorvastatin treatment benefit in atherosclerosis Dotaz Zobrazit nápovědu
Endoglin (a type III TGF-β receptor) is able to modulate ligand binding and signaling by association with the TGF-β type I receptors (ALK-1 and ALK-5). In this study, we hypothesized whether atorvastatin treatment affects endoglin/ALK-1/p-Smad1/VEGF expression in the aorta and endoglin levels in serum in ApoE/LDLR double knockout mice. ApoE/LDLR double knockout mice were fed with a diet containing either 1% of cholesterol (CHOL) or cholesterol with atorvastatin (ATV) at a dose of 50mg/kg/day. Biochemical analysis of cholesterol levels and ELISA analysis of endoglin levels in serum, lesion area size, immunohistochemistry and Western blot analysis in mice aorta were performed. Atorvastatin treatment resulted in a significant decrease of total, VLDL and LDL cholesterol, atherosclerotic lesion size and endoglin serum levels in comparison with CHOL mice. On the other hand, atorvastatin treatment significantly increased the expressions of endoglin by 1431%, ALK-1 by 310%, p-Smad1 by 135% and VEGF by 62% in aorta when compared to CHOL mice. In conclusion, it has been demonstrated that atorvastatin increases endoglin/ALK-1/p-Smad1/VEGF expression in aorta and decreases the size of atherosclerotic lesions, suggesting that activation of this endothelial-protective pathway might support the antiatherogenic effects of atorvastatin. Moreover, atorvastatin concurrently decreased serum levels of endoglin suggesting that monitoring of endoglin levels in blood might represent an important marker of the progression and/or treatment of atherosclerosis.
- MeSH
- aktivinové receptory typu I metabolismus MeSH
- apolipoproteiny E genetika MeSH
- aterosklerotický plát chemicky indukované metabolismus patologie prevence a kontrola MeSH
- ateroskleróza krev chemicky indukované metabolismus patologie prevence a kontrola MeSH
- biomarkery farmakologické krev metabolismus MeSH
- cholesterol dietní farmakologie MeSH
- cholesterol krev MeSH
- fosforylace účinky léků MeSH
- HDL-cholesterol krev MeSH
- intracelulární signální peptidy a proteiny krev metabolismus MeSH
- krev účinky léků MeSH
- kyseliny heptylové farmakologie terapeutické užití MeSH
- LDL-cholesterol krev MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- protein Smad1 metabolismus MeSH
- pyrroly farmakologie terapeutické užití MeSH
- receptory LDL genetika MeSH
- Valsalvův sinus metabolismus patologie MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- VLDL-cholesterol krev MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH