title: Cholesterol effects on endoglin and its downstream pathways in ApoE/LDLR double knockout mice.
abstract: BACKGROUND
  The aim of the study was to evaluate whether cholesterol-rich diet affects transforming growth factor-β-RIII (endoglin) levels in blood and 2 endoglin-related pathways in the aorta of ApoE/LDLR double knockout mice.
  
  
  RESULTS
  Mice were fed either chow diet (CHOW) (n=8) or by 1% cholesterol-rich diet (CHOL) (n=8). Biochemical analysis of cholesterol and endoglin levels in blood, lesion size area, immunohistochemistry and Western blot analysis in mice aortas were performed. Biochemical analysis showed that cholesterol-rich diet resulted in a significant increase of cholesterol and endoglin levels in serum, and increased plaque size in the aorta. In addition, a cholesterol-rich diet significantly decreased the expressions of endoglin by 92%, activin receptor-like kinase (ALK)-1 by 71%, p-Smad2 by 21%, and vascular endothelial growth factor (VEGF) by 37% when compared to CHOW mice, but ALK-5, p-Smad1, and endothelial nitric oxide synthase were not significantly affected.
  
  
  CONCLUSIONS
  Hypercholesterolemia increases endoglin levels in blood and simultaneously decreases its expression in aorta, together with atherosclerosis protective markers p-Smad2 and VEGF, followed by increased plaque size. Inhibition of endoglin signaling might be one of the mechanisms responsible for the promoting of endothelial dysfunction and atherogenesis. Moreover, the monitoring of endoglin serum levels might represent an attractive blood marker of progression of disease; however, the precise source and role of endoglin in blood serum remains to be elucidated.
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Czech Republic.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Strasky
authors.forename: Lenka
authors.initials: L
authors.lastname: Vecerova
authors.forename: Jana
authors.initials: J
authors.lastname: Rathouska
authors.forename: Martina
authors.initials: M
authors.lastname: Slanarova
authors.forename: Eva
authors.initials: E
authors.lastname: Brcakova
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Kudlackova
authors.forename: Ctirad
authors.initials: C
authors.lastname: Andrys
authors.forename: Stanislav
authors.initials: S
authors.lastname: Micuda
authors.forename: Petr
authors.initials: P
authors.lastname: Nachtigal
mesh_terms: D029404:Activin Receptors / Q000378:metabolism; D030201:Activin Receptors, Type I / Q000378:metabolism; D030301:Activin Receptors, Type II; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004195:Disease Models, Animal; D000071063:Endoglin; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051898:Smad1 Protein / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D002791:Cholesterol, Dietary; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011973:Receptors, LDL; D018125:Receptors, Transforming Growth Factor beta; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C498931:Acvrl1 protein, mouse; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse