Published Online
on September 20, 2004

A more recent version of this article appeared on September 28, 2004

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Submitted on November 6, 2003
Revised on May 26, 2004
Accepted on May 28, 2004

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, and 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.

^* To whom correspondence should be addressed. E-mail: morishit{at}cgt.med.osaka-u.ac.jp.

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

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