title: Modification of hyaluronan by heavy chains of inter-α-inhibitor in idiopathic pulmonary arterial hypertension.
abstract: We previously reported an altered hyaluronan (HA) metabolism in idiopathic pulmonary arterial hypertension (IPAH) lung tissue and cultured smooth muscle cells. Hyaluronan was present in the smooth muscle cell layer surrounding the pulmonary vasculature and in plexigenic lesions. Additionally, cultured pulmonary artery smooth muscle cells produced spontaneous HA "cable" structures, without additional stimuli, that were leukocyte-adhesive. We now present evidence that the HA that accumulates in IPAH plexigenic lesions is a pathological form of HA in which heavy chains (HCs) from the serum-derived proteoglycan inter-α-inhibitor are covalently attached to the HA backbone to form a pathological HC-HA complex. CD45-positive leukocytes were identified within these HC-HA matrices. Elevated mRNA levels of the enzyme that transfers HCs to HA, known as tumor necrosis factor-stimulated gene 6, were detected in IPAH lung tissue.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lauer
authors.affiliation: Department of Medical Biology, Faculty of Medicine, and Genome Stem Cell Center, Erciyes University, Melikgazi 38039, Kayseri, Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Aytekin
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: Suzy A
authors.initials: SA
authors.lastname: Comhair
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Loftis
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: Liping
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: Carol F
authors.initials: CF
authors.lastname: Farver
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Hascall
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195; Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, Ohio 44195. Electronic address: dweikr@ccf.org.
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics; D065627:Familial Primary Pulmonary Hypertension; D015870:Gene Expression; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism*
chemical_list: D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid
keywords: Extracellular Matrix; Glycobiology; Heavy Chain; Hyaluronan; Hyaluronate; Inter-α-inhibitor; Lung; Proteoglycan; TSG-6; Tumor Necrosis Factor-stimulated Gene 6