Recombinant adenovirus vector mediated expression of lipoprotein (a) [Lp(a)] in rabbit plasma

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 dis ulfide bond. Apo(a) and apoB-100 are synthesized by the liver and covalentl y associate or couple to form Lp(a) extracellularly. Elevated plasma Lp(a) is an independent risk factor for vascular injury disorders such as resteno sis after balloon angioplasty and accelerated graft atherosclerosis followi ng heart transplantation. Lp(a) is not expressed in laboratory animals maki ng studies of its pathophysiology difficult. To overcome this problem, we e xplored the possibility of generating Lp(a) in rabbit plasma using replicat ion-deficient adenovirus vector mediated gene delivery. Rabbits were chosen because of their large vessels and unlike mouse or rat, rabbit apoB-100 co uld 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) injec tion into the rabbit marginal vein caused the appearance of plasma rLp(a). Injection of a r adenovirus vector expressing the bacterial LacZ gene (Ad-L acZ) 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 us ing adenovirus vector mediated gene transfer. Therefore, this system may be suitable for investigating Lp(a)'s role in the development of vascular inj ury diseases in a rabbit model. (C) 1999 Elsevier Science B.V. All rights r eserved.