This Article Full Text Full Text (PDF) All Versions of this Article: 110/13/1806    most recent 01.CIR.0000142607.33398.54v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Katsuragi, N. Articles by Sugimura, K. Search for Related Content PubMed PubMed Citation Articles by Katsuragi, N. Articles by Sugimura, K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Substance via MeSH Related Collections Other myocardial biology Other heart failure Myocardial cardiomyopathy disease

(Circulation. 2004;110:1806-1813.)
© 2004 American Heart Association, Inc.

Heart Failure

Periostin as a Novel Factor Responsible for Ventricular Dilation

Naruto Katsuragi; Ryuichi Morishita, MD, PhD; Noriko Nakamura, MD; Tayehito Ochiai, PhD; Yoshiaki Taniyama, MD, PhD; Yasuhiro Hasegawa; Kayoko Kawashima; Yasufumi Kaneda, MD, PhD; Toshio Ogihara, MD, PhD; Keijiro Sugimura, PhD

From Daiichi Suntory Biomedical Research Ltd (N.K., N.N., T. Ochiai, Y.H., K.K., K.S.), Osaka; the Divisions of Clinical Gene Therapy (R.M., Y.T.) and of Gene Therapy Science (Y.K.), and the Department of Geriatric Medicine (T. Ogihara), Osaka University Graduate School of Medicine, Suita, Japan.

Correspondence to Naruto Katsuragi, Daiichi Suntory Biomedical Research Ltd, 1-1-1 Wakayamadai Shimamoto-cho, Mishima-gun, Osaka, Japan, or Ryuichi Morishita, Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Japan. E-mail morishit{at}cgt.med.osaka-u.ac.jp

Received November 6, 2003; de novo received April 7, 2004; revision received May 26, 2004; accepted May 28, 2004.

Background— Periostin is highly expressed in the myocardium in patients with heart failure. However, no report has documented the function of periostin. To identify the function of periostin in the pathophysiology of heart failure, overexpression or loss of function of the periostin gene was examined by direct transfection into the rat heart.

Methods and Results— Rats transfected with the periostin gene by the HVJ-liposome method showed left ventricular (LV) dilation as assessed by echocardiography, accompanied by an increase in periostin expression. Consistently significant differences were observed in LV pressure, LV end-diastolic pressure, LV dP/dt_max, and LV dP/dt_min at 6 and 12 weeks after transfection in rats transfected with the periostin gene, accompanied by a decrease in cardiac myocytes and an increase in collagen deposition. Importantly, periostin has the ability to inhibit the spreading of myocytes and the adhesion of cardiac fibroblasts with or without fibronectin. Markers of cardiac dysfunction such as brain natriuretic peptide and endothelin-1 gene expression were significantly increased after transfection in the LV of rats transfected with the periostin gene. These data demonstrate that overexpression of the periostin gene led to cardiac dysfunction. Thus, we examined the inhibition of periostin in Dahl salt-sensitive rats by an antisense strategy because periostin is highly expressed in heart failure. Importantly, inhibition of periostin gene expression resulted in a significant increase in survival rate, accompanied by an improvement of LV function.

Conclusion— The present study demonstrates the contribution of the periostin gene to cardiac dilation in animal models. Inhibition of periostin might become a new therapeutic target for the treatment of heart failure.

Key Words: gene therapy • heart failure • remodeling • adhesion

This article has been cited by other articles:

				I. Banerjee, J. W. Fuseler, A. R. Intwala, and T. A. Baudino IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1694 - H1704. [Abstract] [Full Text] [PDF]

				A. Lorts, J. A. Schwanekamp, J. W. Elrod, M. A. Sargent, and J. D. Molkentin Genetic Manipulation of Periostin Expression in the Heart Does Not Affect Myocyte Content, Cell Cycle Activity, or Cardiac Repair Circ. Res., January 2, 2009; 104(1): e1 - e7. [Abstract] [Full Text] [PDF]

				Y. Imai, H. R. Patel, N. M. Doliba, F. M. Matschinsky, J. W. Tobias, and R. S. Ahima Analysis of gene expression in pancreatic islets from diet-induced obese mice Physiol Genomics, December 12, 2008; 36(1): 43 - 51. [Abstract] [Full Text] [PDF]

				T. Urashima, M. Zhao, R. Wagner, G. Fajardo, S. Farahani, T. Quertermous, and D. Bernstein Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1351 - H1368. [Abstract] [Full Text] [PDF]

				M. S. Penn and A. A. Mangi Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy Circ. Res., June 20, 2008; 102(12): 1471 - 1482. [Abstract] [Full Text] [PDF]

				L. Elsherif, M. S. Huang, S.-Y. Shai, Y. Yang, R. Y. Li, J. Chun, M. A. Mekany, A. L. Chu, S. J. Kaufman, and R. S. Ross Combined Deficiency of Dystrophin and {beta}1 Integrin in the Cardiac Myocyte Causes Myocardial Dysfunction, Fibrosis and Calcification Circ. Res., May 9, 2008; 102(9): 1109 - 1117. [Abstract] [Full Text] [PDF]

				P. Snider, R. B. Hinton, R. A. Moreno-Rodriguez, J. Wang, R. Rogers, A. Lindsley, F. Li, D. A. Ingram, D. Menick, L. Field, et al. Periostin Is Required for Maturation and Extracellular Matrix Stabilization of Noncardiomyocyte Lineages of the Heart Circ. Res., April 11, 2008; 102(7): 752 - 760. [Abstract] [Full Text] [PDF]

				D. P. Kolditz, M. C.E.F. Wijffels, N. A. Blom, A. van der Laarse, N. D. Hahurij, H. Lie-Venema, R. R. Markwald, R. E. Poelmann, M. J. Schalij, and A. C. Gittenberger-de Groot Epicardium-Derived Cells in Development of Annulus Fibrosis and Persistence of Accessory Pathways Circulation, March 25, 2008; 117(12): 1508 - 1517. [Abstract] [Full Text] [PDF]

				M. Shimazaki, K. Nakamura, I. Kii, T. Kashima, N. Amizuka, M. Li, M. Saito, K. Fukuda, T. Nishiyama, S. Kitajima, et al. Periostin is essential for cardiac healingafter acute myocardial infarction J. Exp. Med., February 18, 2008; 205(2): 295 - 303. [Abstract] [Full Text] [PDF]

				T. Oka, J. Xu, R. A. Kaiser, J. Melendez, M. Hambleton, M. A. Sargent, A. Lorts, E. W. Brunskill, G. W. Dorn II, S. J. Conway, et al. Genetic Manipulation of Periostin Expression Reveals a Role in Cardiac Hypertrophy and Ventricular Remodeling Circ. Res., August 3, 2007; 101(3): 313 - 321. [Abstract] [Full Text] [PDF]

				K. Iekushi, Y. Taniyama, J. Azuma, N. Katsuragi, N. Dosaka, F. Sanada, N. Koibuchi, K. Nagao, T. Ogihara, and R. Morishita Novel Mechanisms of Valsartan on the Treatment of Acute Myocardial Infarction Through Inhibition of the Antiadhesion Molecule Periostin Hypertension, June 1, 2007; 49(6): 1409 - 1414. [Abstract] [Full Text] [PDF]

				J. Litvin, X. Chen, S. Keleman, S. Zhu, and M. Autieri Expression and function of periostin-like factor in vascular smooth muscle cells Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1672 - C1680. [Abstract] [Full Text] [PDF]

				J. T. Butcher, S. Tressel, T. Johnson, D. Turner, G. Sorescu, H. Jo, and R. M. Nerem Transcriptional Profiles of Valvular and Vascular Endothelial Cells Reveal Phenotypic Differences: Influence of Shear Stress Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 69 - 77. [Abstract] [Full Text] [PDF]