Published December 22, 2010 - More info
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.
Daihiko Hakuno, Naritaka Kimura, Masatoyo Yoshioka, Makio Mukai, Tokuhiro Kimura, Yasunori Okada, Ryohei Yozu, Chisa Shukunami, Yuji Hiraki, Akira Kudo, Satoshi Ogawa, Keiichi Fukuda
Original citation: J. Clin. Invest. 2010;120(7):2292–2306. doi:10.1172/JCI40973.
Citation for this corrigendum: J. Clin. Invest. 2011;121(1):454. doi:10.1172/JCI45853.
In the Acknowledgments section, a mention of support from the Japan Research Promotion Society for Cardiovascular Diseases was inadvertently omitted. The correct sentence appears below.
This study received support from the program for the Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation (NIBIO; to K. Fukuda), Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to D. Hakuno and K. Fukuda), a Japan Heart Foundation/Novartis Grant for Research Award on Molecular and Cellular Cardiology (to D. Hakuno), a Sakakibara Memorial Research Grant from the Japan Research Promotion Society for Cardiovascular Diseases (to D. Hakuno), and a grant from the Keio Gijuku Fund for the Advancement of Education and Research (to D. Hakuno).
The authors regret the error.