title: Inhibition of neointima formation through DNA vaccination for apolipoprotein(a): a new therapeutic strategy for lipoprotein(a).
abstract: Lipoprotein(a) [Lp(a)] is an unique lipoprotein consisting of the glycoprotein apolipoprotein(a) [apo(a)] in low-density lipoprotein. Although Lp(a) is a well-known independent risk factor for cardiovascular disease; however, there is no drugs to decrease plasma Lp(a) level. Thus, to inhibit the biological activity of Lp(a), we developed DNA vaccine for apo(a) by the targeting to the selected 12 hydrophilic amino acids in the kringle-4 type 2 domain of apo(a). Hepatitis B virus core protein was used as an epitope carrier to enhance the immunogenicity. Intramuscular immunization with apo(a) vaccine resulted in the significant inhibition of neointima formation in carotid artery ligation model using Lp(a) transgenic mice, associated with anti-apo(a) antibody and decrease in vascular Lp(a) deposition. Overall, this study provided the first evidence that the pro-atherosclerotic actions of Lp(a) could be prevented by DNA vaccine directed against apo(a), suggesting a novel therapeutic strategy to treat cardiovascular diseases related to high Lp(a).
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamada-oka Suita, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kyutoku
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koriyama
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nakagami
authors.forename: Munehisa
authors.initials: M
authors.lastname: Shimamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kurinami
authors.forename: Hideki
authors.initials: H
authors.lastname: Tomioka
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyake
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D017270:Lipoprotein(a) / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D058426:Neointima / Q000235:genetics* / Q000628:therapy*; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D001054:Apolipoproteins A; D017270:Lipoprotein(a); D019444:Vaccines, DNA
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