Published Online
on March 25, 2002

A more recent version of this article appeared on April 9, 2002

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Submitted on December 31, 2001
Revised on February 11, 2002
Accepted on February 13, 2002

Accelerated Reendothelialization With Suppressed Thrombogenic Property and Neointimal Hyperplasia of Rabbit Jugular Vein Grafts by Adenovirus-Mediated Gene Transfer of C-Type Natriuretic Peptide

N. Ohno MD, H. Itoh MD, PhD^*, T. Ikeda MD, PhD, K. Ueyama MD, K. Yamahara MD, K. Doi MD, PhD, J. Yamashita MD, PhD, M. Inoue MD, K. Masatsugu MD, N. Sawada MD, PhD, Y. Fukunaga MD, S. Sakaguchi MD, M. Sone MD, T. Yurugi MD, H. Kook MD, PhD, M. Komeda MD, PhD, and K. Nakao MD, PhD

From the Department of Cardiovascular Surgery (N.O., T.I., K.U., M.K.) and the Department of Medicine and Clinical Science (H.I., K.Y., K.D., J.Y., M.I., K.M., N.S., Y.F., S.S., M.S., T.Y., K.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan; and the Department of Pharmacology (H.K.), Chonnam University Medical School, Kwangju, Korea.

^* To whom correspondence should be addressed. E-mail: hiito{at}kuhp.kyoto-u.ac.jp.

Background—Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft.

Methods and Results—Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81±0.05 versus 0.30±0.14, P<0.01) and at 28 days (0.96±0.01 versus 0.45±0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration.

Conclusions—Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Key words: natriuretic peptides • viruses • grafting • genes

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