Endoglin as a possible marker of atorvastatin treatment benefit in atherosclerosis

• Published in: Pharmacological research 2011-07, Vol.64 (1), p.53-59
• Main Authors: Rathouska, Jana, Vecerova, Lenka, Strasky, Zbynek, Slanarova, Martina, Brcakova, Eva, Mullerova, Zuzana, Andrys, Ctirad, Micuda, Stanislav, Nachtigal, Petr
• Format: Article
• Language: English
• Subjects: Activin Receptors, Type I - metabolism; ALK-1; Animals; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - chemically induced; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Atorvastatin; Atorvastatin Calcium; Biomarkers, Pharmacological - blood; Biomarkers, Pharmacological - metabolism; Blood - drug effects; Cholesterol - blood; Cholesterol, Dietary - pharmacology; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Cholesterol, VLDL - blood; Endoglin; Female; Heptanoic Acids - pharmacology; Heptanoic Acids - therapeutic use; Intracellular Signaling Peptides and Proteins - blood; Intracellular Signaling Peptides and Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; p-Smad1; Phosphorylation - drug effects; Plaque, Atherosclerotic - chemically induced; Plaque, Atherosclerotic - metabolism; Plaque, Atherosclerotic - pathology; Plaque, Atherosclerotic - prevention & control; Pyrroles - pharmacology; Pyrroles - therapeutic use; Receptors, LDL - genetics; Sinus of Valsalva - metabolism; Sinus of Valsalva - pathology; Smad1 Protein - metabolism; Vascular Endothelial Growth Factor A - metabolism; VEGF
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2011.03.008

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 50 mg/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.