This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 49/6/1409    most recent HYPERTENSIONAHA.106.080994v1 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 Iekushi, K. Articles by Morishita, R. Search for Related Content PubMed PubMed Citation Articles by Iekushi, K. Articles by Morishita, R. Related Collections Structure Congestive ACE/Angiotension receptors Animal models of human disease Myocardial cardiomyopathy disease Acute myocardial infarction

(Hypertension. 2007;49:1409.)
© 2007 American Heart Association, Inc.

Original Articles

Novel Mechanisms of Valsartan on the Treatment of Acute Myocardial Infarction Through Inhibition of the Antiadhesion Molecule Periostin

Kazuma Iekushi; Yoshiaki Taniyama; Junya Azuma; Naruto Katsuragi; Norio Dosaka; Fumihiro Sanada; Nobutaka Koibuchi; Kaori Nagao; Toshio Ogihara; Ryuichi Morishita

From the Departments of Clinical Gene Therapy (K.I., Y.T., J.A., N.K., N.D., F.S., N.K., K.N., R.M.) and Geriatric Medicine (K.I., Y.T., J.A., N.K., N.D., T.O., R.M.), Graduate School of Medicine, Osaka University, Suita, Japan.

Correspondence to Ryuichi Morishita, Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita 565-0871, Japan. E-mail morishit{at}cgt.med.osaka-u.ac.jp

Our previous study demonstrated that periostin, an extracellular matrix protein, plays an important role in left ventricular remodeling through the inhibition of cell–cell interactions. Because the gene regulation of periostin has not yet been examined, we focused on the effects of angiotensin (Ang) II and mechanical stretch, because Ang II and mechanical stretch are related to cardiac remodeling after myocardial infarction. First, we examined the effects of Ang II on periostin in myocytes and fibroblasts in vitro. Ang II significantly increased periostin through phosphatidylinositol 3-kinase, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase 1/2 pathways in myocytes and fibroblasts (P<0.05). On the other hand, mechanical stretch also significantly increased periostin expression (P<0.05). This increase was inhibited partially, but significantly, by an Ang II receptor blocker, valsartan, and inhibited almost completely by valsartan with the neutralization antibodies for transforming growth factor-ß and platelet-derived growth factor–BB (P<0.05). Therefore, we further examined periostin expression in vivo. Periostin expression was significantly increased in infarcted myocardium (P<0.05), and treatment with valsartan significantly attenuated it at 4 weeks after myocardial infarction (P<0.05), accompanied by a significant improvement in cardiac dysfunction (P<0.05). Overall, the present study demonstrated that Ang II, as well as mechanical stretch, stimulated periostin expression in both cardiac myocytes and fibroblasts, whereas valsartan significantly attenuated the increase in periostin expression. The inhibition of periostin by valsartan might especially contribute to its beneficial effects on cardiac remodeling after myocardial infarction.

Key Words: angiotensin II type 1 receptor blockers • myocardial infarction • adhesions • fibrosis • ventricular remodeling

This article has been cited by other articles:

				P. Snider, K. N. Standley, J. Wang, M. Azhar, T. Doetschman, and S. J. Conway Origin of Cardiac Fibroblasts and the Role of Periostin Circ. Res., November 6, 2009; 105(10): 934 - 947. [Abstract] [Full Text] [PDF]

				F. Sanada, Y. Taniyama, K. Iekushi, J. Azuma, K. Okayama, H. Kusunoki, N. Koibuchi, T. Doi, Y. Aizawa, and R. Morishita Negative Action of Hepatocyte Growth Factor/c-Met System on Angiotensin II Signaling via Ligand-Dependent Epithelial Growth Factor Receptor Degradation Mechanism in Vascular Smooth Muscle Cells Circ. Res., September 25, 2009; 105(7): 667 - 675. [Abstract] [Full Text] [PDF]

				F. Sanada, Y. Taniyama, J. Azuma, K. Iekushi, N. Dosaka, T. Yokoi, N. Koibuchi, H. Kusunoki, Y. Aizawa, and R. Morishita Hepatocyte Growth Factor, but not Vascular Endothelial Growth Factor, Attenuates Angiotensin II-Induced Endothelial Progenitor Cell Senescence Hypertension, January 1, 2009; 53(1): 77 - 82. [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]

				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. K. Borg and R. Markwald Periostin: More Than Just an Adhesion Molecule Circ. Res., August 3, 2007; 101(3): 230 - 231. [Full Text] [PDF]