title: Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents.
abstract: Valvular heart disease (VHD) is the term given to any disease process involving one or more of the heart valves. The condition can be congenital or acquired, for example as a result of atherosclerosis or rheumatic fever. Despite its clinical importance, the molecular mechanisms underlying VHD remain unknown. We investigated the pathophysiologic role and molecular mechanism of periostin, a protein that plays critical roles in cardiac valve development, in degenerative VHD. Unexpectedly, we found that periostin levels were drastically increased in infiltrated inflammatory cells and myofibroblasts in areas of angiogenesis in human atherosclerotic and rheumatic VHD, whereas periostin was localized to the subendothelial layer in normal valves. The expression patterns of periostin and chondromodulin I, an angioinhibitory factor that maintains cardiac valvular function, were mutually exclusive. In WT mice, a high-fat diet markedly increased aortic valve thickening, annular fibrosis, and MMP-2 and MMP-13 expression levels, concomitant with increased periostin expression; these changes were attenuated in periostin-knockout mice. In vitro and ex vivo studies revealed that periostin promoted tube formation and mobilization of ECs. Furthermore, periostin prominently increased MMP secretion from cultured valvular interstitial cells, ECs, and macrophages in a cell type-specific manner. These findings indicate that, in contrast to chondromodulin I, periostin plays an essential role in the progression of cardiac valve complex degeneration by inducing angiogenesis and MMP production.
authors.affiliation: Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Daihiko
authors.initials: D
authors.lastname: Hakuno
authors.forename: Naritaka
authors.initials: N
authors.lastname: Kimura
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Makio
authors.initials: M
authors.lastname: Mukai
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yozu
authors.forename: Chisa
authors.initials: C
authors.lastname: Shukunami
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiraki
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D006349:Heart Valve Diseases / Q000378:metabolism* / Q000503:physiopathology*; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012214:Rheumatic Heart Disease / Q000378:metabolism; D012377:Rodentia / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D020782:Matrix Metalloproteinases