title: Type I and type III collagen synthesis and composition in the valve matrix in aortic valve stenosis.
abstract: Changes in the collagenous matrix may contribute to the pathogenesis and progression of human aortic valve stenosis (AS). To evaluate the significance of collagen I and III in the pathogenesis of AS, we studied their synthesis in diseased valves. Type I and type III collagen mRNA expression and the immunohistochemical localization of the collagen antigens were studied from 36 AS and 2 normal aortic valves. The concentrations of propeptides and telopeptide structure of type I (PINP, PICP, and ICTP) and those of III collagens (PIIINP and IIINTP) were measured by radioimmunoassays in soluble tissue extracts and trypsin-solubilized calcified and non-calcified matrices of 11 AS and 24 healthy aortic valves of different ages. The synthesis of type I collagen, localized in the myofibroblasts adjacent to calcified nodules, was two- to three-fold in the AS samples compared to the controls. The proportion of collagen in the total protein fraction was 90% in the healthy valves, 50% in the non-calcified matrix, and 10% in the calcified matrix of AS valves. In the calcified valves, the ICTP content was six-fold compared to the age-matched controls and two-fold compared to the young control group. In the controls, the amount of ICTP in type I collagen decreased with age (r=-0.908, p<0.001) and was replaced by other cross-linked C-telopeptide structure. The concentration of type III collagen decreased during aging (r=-0.753, p<0.001). The decrease in total collagen content, despite the increase in type I collagen synthesis indicates an increase in collagen turnover in AS. The calcification of the aortic valves is accompanied by increased amount of ICTP in type I collagen.
authors.affiliation: Department of Clinical Chemistry, University of Oulu, Oulu, Finland.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Eriksen
authors.forename: Jari
authors.initials: J
authors.lastname: Satta
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
authors.forename: Mikko
authors.initials: M
authors.lastname: Veijola
authors.forename: Päivi
authors.initials: P
authors.lastname: Väre
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D001024:Aortic Valve Stenosis / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III; D010455:Peptides; D012333:RNA, Messenger; C052929:collagen type I trimeric cross-linked peptide