Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents

Daihiko Hakuno, Naritaka Kimura, Masatoyo Yoshioka, Makio Mukai, Tokuhiro Kimura, Yasunori Okada, Ryohei Yozu, Chisa Shukunami, Yuji Hiraki, Akira Kudo, Satoshi Ogawa, Keiichi Fukuda

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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.

Original languageEnglish
Pages (from-to)2292-2306
Number of pages15
JournalJournal of Clinical Investigation
Volume120
Issue number7
DOIs
Publication statusPublished - 2010 Jul 1

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Heart Valve Diseases
Heart Valves
Matrix Metalloproteinases
Rodentia
Rheumatic Heart Disease
Myofibroblasts
Rheumatic Fever
High Fat Diet
Aortic Valve
Knockout Mice
Atherosclerosis
Fibrosis
Macrophages
Proteins

ASJC Scopus subject areas

  • Medicine(all)

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Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents. / Hakuno, Daihiko; Kimura, Naritaka; Yoshioka, Masatoyo; Mukai, Makio; Kimura, Tokuhiro; Okada, Yasunori; Yozu, Ryohei; Shukunami, Chisa; Hiraki, Yuji; Kudo, Akira; Ogawa, Satoshi; Fukuda, Keiichi.

In: Journal of Clinical Investigation, Vol. 120, No. 7, 01.07.2010, p. 2292-2306.

Research output: Contribution to journalArticle

Hakuno, Daihiko ; Kimura, Naritaka ; Yoshioka, Masatoyo ; Mukai, Makio ; Kimura, Tokuhiro ; Okada, Yasunori ; Yozu, Ryohei ; Shukunami, Chisa ; Hiraki, Yuji ; Kudo, Akira ; Ogawa, Satoshi ; Fukuda, Keiichi. / Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents. In: Journal of Clinical Investigation. 2010 ; Vol. 120, No. 7. pp. 2292-2306.
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