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(Hypertension. 2003;41:302.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Adrenomedullin Overexpression to Inhibit Cuff-Induced Arterial Intimal Formation

Masao Yamasaki; Junsuke Kawai; Takashi Nakaoka; Teruhiko Ogita; Akihiro Tojo; Toshiro Fujita

From the Department of Internal Medicine, Faculty of Medicine (M.Y., T.O., A.T., T.F.), Department of Plastic and Reconstructive Surgery, Faculty of Medicine (J.K.), and Department of Advanced Medicine, Institute of Medical Science (T.N.), University of Tokyo, Tokyo, Japan.

Correspondence to Toshiro Fujita, Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail fujita-dis{at}h.u-tokyo.ac.jp

Adrenomedullin (AM) inhibits vascular smooth muscle cell proliferation stimulated by fetal calf serum and platelet-derived growth factor in vitro. In this study, an adenovirus expressing AM (AxCAAM) was created to examine the in vivo action of AM. Femoral arteries of Wistar rats were wrapped with a silicone cuff and treated with adenovirus expressing Escherichia coli ß-galactosidase (AxCALacZ) or AxCAAM. Immunoreactivity for endothelial nitric oxide synthase (eNOS) was reduced in the endothelium of cuff-injured arteries and was associated with increased local DNA synthesis. Consequently, the intimal formation measured by the intimal-to-medial ratio was significantly increased at 14 and 28 days after the cuff placement. AxCAAM-infected arteries increased the expression of eNOS in the endothelium and inducible NOS in the media and the adventitia. AxCAAM significantly decreased the intimal-to-medial ratio by 40% at 14 days and 51% at 28 days, whereas AxCALacZ showed no changes compared with cuff-injured control arteries. AM overexpression effectively limits intimal hyperplasia by reducing cell proliferation through a nitric oxide–dependent pathway of eNOS. Our findings suggest the possibility of a therapeutic use of the AM gene for the prevention of vascular proliferative disorders.

Key Words: adrenomedullin • muscle, smooth, vascular • endothelium • nitric oxide synthase

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