Atorvastatin Increases Endoglin, SMAD2, Phosphorylated SMAD2/3 and eNOS Expression in ApoE/LDLR Double Knockout Mice

Aim: Endoglin is a homodimeric transmembrane glycoprotein that has been demonstrated to affect transforming growth factor β (TGF-β) signaling and endothelial nitric oxide synthase (eNOS) expression by affecting SMAD proteins in vitro. Thus, in this study we stepped forward to elucidate whether endog...

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Bibliographic Details
Published in:Journal of Atherosclerosis and Thrombosis 2009, Vol.16(3), pp.265-274
Main Authors: Nachtigal, Petr, Pospisilova, Nada, Vecerova, Lenka, Micuda, Stanislav, Brcakova, Eva, Pospechova, Katerina, Semecky, Vladimir
Format: Article
Language:English
Subjects:
Animals
Anticholesteremic Agents - pharmacology
Aorta - chemistry
ApoE/LDLR double knockout mice
Apolipoproteins E - genetics
Atherosclerosis - metabolism
Atorvastatin
Blotting, Western
Endoglin
Endothelium, Vascular - chemistry
eNOS
Female
Heptanoic Acids - pharmacology
Immunohistochemistry
Intracellular Signaling Peptides and Proteins - analysis
Mice
Mice, Knockout
Nitric Oxide Synthase Type III - analysis
Phosphorylated SMAD2/3
Phosphorylation
Pyrroles - pharmacology
Receptors, LDL - genetics
SMAD2
Smad2 Protein - analysis
Smad3 Protein - analysis
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Summary:Aim: Endoglin is a homodimeric transmembrane glycoprotein that has been demonstrated to affect transforming growth factor β (TGF-β) 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.
ISSN:1340-3478
1880-3873
DOI:10.5551/jat.E745