BACKGROUND: While the prevalence of calcified aortic valve disease continues to rise and no pharmacological treatments exist, little is known regarding the pathogenesis of the disease. Proteoglycans and the glycosaminoglycan hyaluronan are involved in calcification in arteriosclerosis and their characterization in calcified aortic valves may lend insight into the pathogenesis of the disease. METHODS: Fourteen calcified aortic valves removed during valve replacement surgery were immunohistochemically stained for the proteoglycans decorin, biglycan, and versican, as well as the glycosaminoglycan hyaluronan. Staining intensity was evaluated in the following regions of interest: center of calcified nodule, edge of nodule, tissue directly surrounding the nodule; center and tissue surrounding small "prenodules"; and fibrosa layer of normal regions of the leaflet distanced from the nodule. RESULTS: Decorin, biglycan, and versican, as well as hyaluronan, were abundantly present immediately surrounding the calcified nodules, but minimally within the nodule itself. Expression of decorin and biglycan in and surrounding prenodules was greater than in the edge and center regions of mature nodules. The levels of expression of the proteoglycans and hyaluronan were highly correlated with one another in the different regions of the valve. CONCLUSIONS: The three proteoglycans and hyaluronan demonstrated distinctive localization relative to nodules within calcified aortic valves, where they likely mediate lipid retention, cell proliferation, and extracellular matrix remodeling, and motivate further study. Comparisons between expression of these components in mature nodules and prenodules suggest distinct roles for these components in nodule progression, especially in the tissues surrounding the nodules.
BACKGROUND: While the prevalence of calcified aortic valve disease continues to rise and no pharmacological treatments exist, little is known regarding the pathogenesis of the disease. Proteoglycans and the glycosaminoglycanhyaluronan are involved in calcification in arteriosclerosis and their characterization in calcified aortic valves may lend insight into the pathogenesis of the disease. METHODS: Fourteen calcified aortic valves removed during valve replacement surgery were immunohistochemically stained for the proteoglycans decorin, biglycan, and versican, as well as the glycosaminoglycanhyaluronan. Staining intensity was evaluated in the following regions of interest: center of calcified nodule, edge of nodule, tissue directly surrounding the nodule; center and tissue surrounding small "prenodules"; and fibrosa layer of normal regions of the leaflet distanced from the nodule. RESULTS:Decorin, biglycan, and versican, as well as hyaluronan, were abundantly present immediately surrounding the calcified nodules, but minimally within the nodule itself. Expression of decorin and biglycan in and surrounding prenodules was greater than in the edge and center regions of mature nodules. The levels of expression of the proteoglycans and hyaluronan were highly correlated with one another in the different regions of the valve. CONCLUSIONS: The three proteoglycans and hyaluronan demonstrated distinctive localization relative to nodules within calcified aortic valves, where they likely mediate lipid retention, cell proliferation, and extracellular matrix remodeling, and motivate further study. Comparisons between expression of these components in mature nodules and prenodules suggest distinct roles for these components in nodule progression, especially in the tissues surrounding the nodules.
Authors: Luis M Moura; Sandra F Ramos; José L Zamorano; Isabel M Barros; Luis F Azevedo; Francisco Rocha-Gonçalves; Nalini M Rajamannan Journal: J Am Coll Cardiol Date: 2007-01-22 Impact factor: 24.094
Authors: Benjamin Müller; Christian Prante; Martin Gastens; Joachim Kuhn; Knut Kleesiek; Christian Götting Journal: Matrix Biol Date: 2007-10-09 Impact factor: 11.583
Authors: S Itoh; M Matubara; T Kawauchi; H Nakamura; S Yukitake; S Ichinose; K Shinomiya Journal: J Mater Sci Mater Med Date: 2001-07 Impact factor: 3.896
Authors: Salma Ayoub; Giovanni Ferrari; Robert C Gorman; Joseph H Gorman; Frederick J Schoen; Michael S Sacks Journal: Compr Physiol Date: 2016-09-15 Impact factor: 9.090
Authors: Salma Ayoub; Chung-Hao Lee; Kathryn H Driesbaugh; Wanda Anselmo; Connor T Hughes; Giovanni Ferrari; Robert C Gorman; Joseph H Gorman; Michael S Sacks Journal: J R Soc Interface Date: 2017-10 Impact factor: 4.118
Authors: Elizabeth H Stephens; Jerome G Saltarrelli; Liezl R Balaoing; L Scott Baggett; Indrajit Nandi; Kristin M Anderson; Joel D Morrisett; Michael J Reardon; Melanie A Simpson; Paul H Weigel; Elizabeth A Olmsted-Davis; Alan R Davis; K Jane Grande-Allen Journal: Pathol Res Pract Date: 2012-09-25 Impact factor: 3.250
Authors: Edward B Neufeld; Leah M Zadrozny; Darci Phillips; Angel Aponte; Zu-Xi Yu; Robert S Balaban Journal: Atherosclerosis Date: 2014-01-08 Impact factor: 5.162
Authors: Rui Song; Lihua Ao; Ke-Seng Zhao; Daniel Zheng; Neil Venardos; David A Fullerton; Xianzhong Meng Journal: Inflamm Res Date: 2014-05-30 Impact factor: 4.575
Authors: Florian Schlotter; Arda Halu; Shinji Goto; Mark C Blaser; Simon C Body; Lang H Lee; Hideyuki Higashi; Daniel M DeLaughter; Joshua D Hutcheson; Payal Vyas; Tan Pham; Maximillian A Rogers; Amitabh Sharma; Christine E Seidman; Joseph Loscalzo; Jonathan G Seidman; Masanori Aikawa; Sasha A Singh; Elena Aikawa Journal: Circulation Date: 2018-07-24 Impact factor: 29.690