HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 Add to Personal Folders Download to citation manager Author home page(s): Yoshiki Sawa Norihide Fukushima Shigeaki Ohtake Hikaru Matsuda Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Suhara, H. Articles by Matsuda, H. Search for Related Content PubMed PubMed Citation Articles by Suhara, H. Articles by Matsuda, H. Related Collections Lung - other

J Thorac Cardiovasc Surg 2002;123:855-861
© 2002 The American Association for Thoracic Surgery

General Thoracic Surgery (GTS)

Gene transfer of human prostacyclin synthase into the liver is effective for the treatment of pulmonary hypertension in rats

From the Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine,^a and the Department of Pharmacology, The National Cardiovascular Center Research Institute,^b Osaka, Japan.

Received for publication May 29, 2001. Revisions requested July 13, 2001. Accepted for publication July 13, 2001. Address for reprints: Yoshiki Sawa, MD, Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan (E-mail: sawa{at}surg1.med.osaka-u.ac.jp).

Background: As one of the future strategies of advanced pulmonary hypertension, intrinsic prostacyclin drug delivery using gene therapy may be useful. We investigated whether transfer of the prostacyclin synthase gene into the liver could ameliorate monocrotaline-induced pulmonary hypertension in rats.
Methods: The human prostacyclin synthase gene was transfected into the liver of rats with monocrotaline-induced pulmonary hypertension. Hemodynamic indices, blood samples, lung tissues, and survival curves were evaluated between rats receiving the gene and control rats.
Results: High levels of prostacyclin synthase gene expression were found in the hepatocytes of the prostacyclin synthase group. The level of 6-keto-prostaglandin F₁ was significantly higher in the prostacyclin synthase group (prostacyclin synthase, 35.4 ± 4.4 ng/mL; control, 22.3 ± 3.3 ng/mL; P = .0436). The right ventricular/femoral artery pressure ratio was significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 0.60 ± 0.039; control, 0.88 ± 0.051; P = .0036). The endothelin-1 levels in the lung tissues were significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 10.42 ± 2.01 pg/mg protein; control, 19.94 ± 2.82 pg/mg protein; P = .0176). The survival ratio was significantly higher in the prostacyclin synthase group than the control group (P = .0375).
Conclusion: This drug delivery system using gene transfer can be considered as an alternative for continuous intravenous prostacyclin infusion for pulmonary hypertension.

This article has been cited by other articles:

				C. Gillio-Meina, S. H. Phang, J. P Mather, B. S Knight, and T. G Kennedy Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization Reproduction, March 1, 2009; 137(3): 537 - 552. [Abstract] [Full Text] [PDF]

				T. Ito, T. Okada, J. Mimuro, H. Miyashita, R. Uchibori, M. Urabe, H. Mizukami, A. Kume, M. Takahashi, U. Ikeda, et al. Adenoassociated Virus Mediated Prostacyclin Synthase Expression Prevents Pulmonary Arterial Hypertension in Rats Hypertension, September 1, 2007; 50(3): 531 - 536. [Abstract] [Full Text] [PDF]

				M. Ono, Y. Sawa, N. Fukushima, H. Suhara, T. Nakamura, C. Yokoyama, T. Tanabe, and H. Matsuda Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats Eur. J. Cardiothorac. Surg., December 1, 2004; 26(6): 1092 - 1097. [Abstract] [Full Text] [PDF]