title: Reduced perlecan expression and accumulation in human carotid atherosclerotic lesions.
abstract: Heparan sulfate in the extracellular matrix of the artery wall has been proposed to possess anti-atherogenic properties by interfering with lipoprotein retention, suppression of inflammation, and inhibition of smooth muscle cell growth. Previously, the amount of heparan sulfate in atherosclerotic lesions from humans and animals has been shown to be reduced but the identity or identities of the heparan sulfate molecules being down regulated in this disease are not known. In this study, atherosclerotic lesions were retrieved from 44 patients undergoing surgery for symptomatic carotid stenosis. Normal iliac arteries from organ donors were used as controls. Analysis of the specimens by gene microarray showed a selective reduction in perlecan gene expression, whereas, expression of the other heparan sulfate proteoglycans in the artery wall, agrin and collagen XVIII, remained unchanged. Expression of the large chondroitin sulfate proteoglycan, versican, also remained unchanged. Real-time PCR confirmed the decrease in perlecan gene expression and the unchanged expression of versican. The findings were supported by immunohistochemical analysis demonstrating a reduced accumulation of both perlecan core protein and heparan sulfate in carotid lesions. The study demonstrates a reduction of perlecan mRNA-expression and protein deposition in human atherosclerosis, which in part explains the low levels of heparan sulfate in this disease.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. kiet.tran@kirurgi.ki.se
authors.forename: Phan-Kiet
authors.initials: PK
authors.lastname: Tran
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Agardh
authors.forename: Karin
authors.initials: K
authors.lastname: Tran-Lundmark
authors.forename: Johan
authors.initials: J
authors.lastname: Ekstrand
authors.forename: Joy
authors.initials: J
authors.lastname: Roy
authors.forename: Bimma
authors.initials: B
authors.lastname: Henderson
authors.forename: Anders
authors.initials: A
authors.lastname: Gabrielsen
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
authors.forename: Jesper
authors.initials: J
authors.lastname: Swedenborg
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Paulsson-Berne
authors.forename: Ulf
authors.initials: U
authors.lastname: Hedin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000235:genetics* / Q000473:pathology*; D016893:Carotid Stenosis / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification
chemical_list: D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D012313:RNA; C071927:perlecan