title: Endoglin as a possible marker of atorvastatin treatment benefit in atherosclerosis.
abstract: 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.
authors: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 500 05, Czech Republic.
authors: Jana
authors: J
authors: Rathouska
authors: Lenka
authors: L
authors: Vecerova
authors: Zbynek
authors: Z
authors: Strasky
authors: Martina
authors: M
authors: Slanarova
authors: Eva
authors: E
authors: Brcakova
authors: Zuzana
authors: Z
authors: Mullerova
authors: Ctirad
authors: C
authors: Andrys
authors: Stanislav
authors: S
authors: Micuda
authors: Petr
authors: P
authors: Nachtigal
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D030301:Activin Receptors, Type II; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000069059:Atorvastatin; D054316:Biomarkers, Pharmacological / Q000097:blood* / Q000378:metabolism; D001769:Blood / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D000071063:Endoglin; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects; D058226:Plaque, Atherosclerotic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000235:genetics; D012850:Sinus of Valsalva / Q000378:metabolism / Q000473:pathology; D051898:Smad1 Protein / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D054316:Biomarkers, Pharmacological; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D000071063:Endoglin; C502004:Eng protein, mouse; D006538:Heptanoic Acids; D047908:Intracellular Signaling Peptides and Proteins; D011758:Pyrroles; D011973:Receptors, LDL; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D002784:Cholesterol; D000069059:Atorvastatin; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C498931:Acvrl1 protein, mouse