부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.atherosclerosis.2004.10.025 Byline: Paivi Turunen (a), Hanna Puhakka (a), Juha Rutanen (a), Mikko O. Hiltunen (a), Tommi Heikura (a), Marcin Gruchala (a), Seppo Yla-Herttuala (a)(b)(c) Keywords: Lipoprotein-associated phospholipase A.sub.2; Adenovirus; Restenosis; Gene transfer Abstract: Postangioplasty restenosis is a multifactorial process and involves mechanisms such as inflammation and stimulation of the expression of growth factors. Lipoprotein-associated phospholipase A.sub.2 (Lp-PLA.sub.2) can modify inflammatory responses by hydrolyzing phospholipids with shortened and/or oxidized sn-2 residues. In this study, we tested a hypothesis that adenovirus-mediated Lp-PLA.sub.2 gene transfer can reduce restenosis in rabbits. Aortas of cholesterol-fed NZW rabbits were balloon-denuded and intra-arterial gene transfer was performed using Dispatch catheter with Lp-PLA.sub.2 or LacZ adenoviruses (1.15x10.sup.10 pfu). Intima/media ratio (I/M), histology and cell proliferation were analyzed. Two weeks after the gene transfer I/M in the LacZ-transduced control group was 0.45[+ or -]0.05 but Lp-PLA.sub.2 gene transfer reduced I/M to 0.25[+ or -]0.03. At four weeks time point I/M in the Lp-PLA.sub.2 group (0.34[+ or -]0.05) was also lower than in the LacZ group (0.53[+ or -]0.06). Plasma Lp-PLA.sub.2 activity was increased in the Lp-PLA.sub.2 group (48.2[+ or -]4.2) as compared to the LacZ group (33.6[+ or -]3.51) at two weeks time point. Transgene expression was detected in the arterial wall two and four weeks after the procedure. Apoptosis was higher in the control vessels than in the Lp-PLA.sub.2 group at two weeks time point. In conclusion, local adenovirus-mediated Lp-PLA.sub.2 gene transfer resulted in a significant reduction in neointima formation in balloon-denuded rabbit aorta and may be useful for the prevention of restenosis after arterial manipulations. Author Affiliation: (a) A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland (b) Department of Medicine, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland (c) Gene Therapy Unit, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland Article History: Received 4 June 2004; Revised 1 September 2004; Accepted 11 October 2004