title: Evidence of deregulated cholesterol efflux in abdominal aortic aneurysm.
abstract: Previous studies indicated that lipids may be associated with abdominal aortic aneurysm (AAA); however the molecular mechanism involved is unclear. Our study aimed to investigate the expression pattern of cholesterol efflux related proteins in AAA. Liver X receptors (LXRα and LXRβ), ATP-binding-cassette transporter A1 (ABCA1), Apolipoprotein AI (ApoAI), smooth muscle α-actin (α-SM) and vimentin expression levels were evaluated in human AAA, atherosclerotic (ATH) and normal abdominal aortic tissues. We found significant differences in LXRα, LXRβ and ABCA1 mRNA expression levels between AAA, ATH and normal whole aortic tissues and also within the AAA, ATH and normal "intima-media" layers. Specifically, LXRα, LXRβ and ABCA1 mRNA levels were decreased in AAA compared to ATH-whole tissues, as well as in AAA "intima-media" compared to ATH and normal "intima-media" layers. Moreover, immunohistochemical evaluation revealed that LXRα and ABCA1 immunoreactivities (IR) were reduced in the AAA media compared to the normal and ATH media layers and that they were also reduced in the intima layer of AAA and ATH tissues, whereas ApoAI-IR was increased in the AAA and ATH aortic walls compared to normal pointing to possible deregulation of the cholesterol efflux mechanism in AAA. Furthermore, double staining for vimentin and α-SM showed vimentin expression in the intima and inner media layer of AAA with sparse vimentin positive SMCs designating possible SMCs phenotype switch from contractile to synthetic form. In addition, histochemical analysis showed excessive lipid accumulation in the AAA wall, while co-staining using Oil Red O with α-SM or CD68 revealed lipid accumulation in SMCs and macrophages, respectively. Our study provides novel evidence for impaired cholesterol efflux in AAA associated with lipid accumulation in SMCs and macrophages, as well as switch of SMCs phenotype from contractile to synthetic form.
authors.affiliation: University of Thessaly, Faculty of Medicine, Department of Cytogenetics and Molecular Genetics, Biopolis, Larissa 41100, Greece.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Mourmoura
authors.affiliation: University of Thessaly, Faculty of Medicine, Department of Pharmacology, Biopolis, Larissa 41100, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Vasilaki
authors.affiliation: University of Thessaly, Faculty of Medicine, Department of Vascular Surgery, Mezourlo, Larissa 41100, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Giannoukas
authors.affiliation: University of Crete, Faculty of Medicine, Department of Forensic Sciences, Heraklion 71110, Crete, Greece.
authors.forename: Emmanouel
authors.initials: E
authors.lastname: Michalodimitrakis
authors.affiliation: Democritus University of Thrace, Faculty of Medicine, Department of Forensic Medicine, Alexandroupolis 68100, Greece.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Pavlidis
authors.affiliation: University of Thessaly, Faculty of Medicine, Department of Cytogenetics and Molecular Genetics, Biopolis, Larissa 41100, Greece; University of Thessaly, Faculty of Medicine, Department of Biology, Biopolis, Larissa 41100, Greece. Electronic address: atsezou@med.uth.gr.
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D005487:Foam Cells / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D057093:Orphan Nuclear Receptors / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D002784:Cholesterol
keywords: ABCA1; Abdominal aortic aneurysm; ApoAI; Cholesterol efflux; LXR; Vimentin