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

研究成果: Article

115 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)2292-2306
ページ数15
ジャーナルJournal of Clinical Investigation
120
発行部数7
DOI
出版物ステータスPublished - 2010 7 1

Fingerprint

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)

これを引用

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.

:: Journal of Clinical Investigation, 巻 120, 番号 7, 01.07.2010, p. 2292-2306.

研究成果: Article

Hakuno, D, Kimura, N, Yoshioka, M, Mukai, M, Kimura, T, Okada, Y, Yozu, R, Shukunami, C, Hiraki, Y, Kudo, A, Ogawa, S & Fukuda, K 2010, 'Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents', Journal of Clinical Investigation, 巻. 120, 番号 7, pp. 2292-2306. https://doi.org/10.1172/JCI40973
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. :: Journal of Clinical Investigation. 2010 ; 巻 120, 番号 7. pp. 2292-2306.
@article{5f7b948652754a3f98983b3f31857d9d,
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.",
author = "Daihiko Hakuno and Naritaka Kimura and Masatoyo Yoshioka and Makio Mukai and Tokuhiro Kimura and Yasunori Okada and Ryohei Yozu and Chisa Shukunami and Yuji Hiraki and Akira Kudo and Satoshi Ogawa and Keiichi Fukuda",
year = "2010",
month = "7",
day = "1",
doi = "10.1172/JCI40973",
language = "English",
volume = "120",
pages = "2292--2306",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "7",

}

TY - JOUR

T1 - Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents

AU - Hakuno, Daihiko

AU - Kimura, Naritaka

AU - Yoshioka, Masatoyo

AU - Mukai, Makio

AU - Kimura, Tokuhiro

AU - Okada, Yasunori

AU - Yozu, Ryohei

AU - Shukunami, Chisa

AU - Hiraki, Yuji

AU - Kudo, Akira

AU - Ogawa, Satoshi

AU - Fukuda, Keiichi

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77954992963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954992963&partnerID=8YFLogxK

U2 - 10.1172/JCI40973

DO - 10.1172/JCI40973

M3 - Article

C2 - 20551517

AN - SCOPUS:77954992963

VL - 120

SP - 2292

EP - 2306

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 7

ER -