Atorvastatin Increases Endoglin, SMAD2, Phosphorylated SMAD2/3 and eNOS Expression in ApoE/LDLR Double Knockout Mice
Language English Country Japan Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19556713
DOI
10.5551/jat.e745
PII: JST.JSTAGE/jat/E745
Knihovny.cz E-resources
- MeSH
- Anticholesteremic Agents pharmacology MeSH
- Aorta chemistry MeSH
- Apolipoproteins E genetics MeSH
- Atherosclerosis metabolism MeSH
- Atorvastatin MeSH
- Endothelium, Vascular chemistry MeSH
- Endoglin MeSH
- Phosphorylation MeSH
- Immunohistochemistry MeSH
- Intracellular Signaling Peptides and Proteins analysis MeSH
- Heptanoic Acids pharmacology MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Smad2 Protein analysis MeSH
- Smad3 Protein analysis MeSH
- Pyrroles pharmacology MeSH
- Receptors, LDL genetics MeSH
- Nitric Oxide Synthase Type III analysis MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anticholesteremic Agents MeSH
- Apolipoproteins E MeSH
- Atorvastatin MeSH
- Endoglin MeSH
- Eng protein, mouse MeSH Browser
- Intracellular Signaling Peptides and Proteins MeSH
- Heptanoic Acids MeSH
- Smad2 Protein MeSH
- Smad3 Protein MeSH
- Pyrroles MeSH
- Receptors, LDL MeSH
- Smad2 protein, mouse MeSH Browser
- Smad3 protein, mouse MeSH Browser
- Nitric Oxide Synthase Type 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.
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