title: Recombinant adenovirus vector mediated expression of lipoprotein (a) [Lp(a)] in rabbit plasma.
abstract: Lipoprotein (a) [Lp(a)] is a heterodimer of apolipoprotein (a) [apo(a)] and apolipoprotein B-100 (apoB-100) of low density lipoprotein linked by a disulfide bond. Apo(a) and apoB-100 are synthesized by the liver and covalently associate or couple to form Lp(a) extracellularly. Elevated plasma Lp(a) is an independent risk factor for vascular injury disorders such as restenosis after balloon angioplasty and accelerated graft atherosclerosis following heart transplantation. Lp(a) is not expressed in laboratory animals making studies of its pathophysiology difficult. To overcome this problem, we explored the possibility of generating Lp(a) in rabbit plasma using replication-deficient adenovirus vector mediated gene delivery. Rabbits were chosen because of their large vessels and unlike mouse or rat, rabbit apoB-100 could interact with apo(a) to generate Lp(a). The recombinant (r) adenovirus vector construct used encoded a 200 kDa apo(a) [Ad-apo(a)]. Ad-apo(a) injection into the rabbit marginal vein caused the appearance of plasma rLp(a). Injection of a r adenovirus vector expressing the bacterial LacZ gene (Ad-LacZ) or PBS (vehicle) did not result in detectable plasma rLp(a). These are the first results to demonstrate plasma expression of rLp(a) in rabbits using adenovirus vector mediated gene transfer. Therefore, this system may be suitable for investigating Lp(a)'s role in the development of vascular injury diseases in a rabbit model.
authors.affiliation: Department of Cardiovascular Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. randy.ramharack@wl.com
authors.forename: R
authors.initials: R
authors.lastname: Ramharack
authors.forename: T M
authors.initials: TM
authors.lastname: Bocan
authors.forename: M J
authors.initials: MJ
authors.lastname: Imperiale
authors.forename: M A
authors.initials: MA
authors.lastname: Spahr
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D053299:Apolipoprotein B-100; D001054:Apolipoproteins A / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D002478:Cells, Cultured; D005822:Genetic Vectors / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007275:Injections, Intravenous; D017270:Lipoprotein(a) / Q000096:biosynthesis* / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D011817:Rabbits
chemical_list: D053299:Apolipoprotein B-100; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D017270:Lipoprotein(a)