Apolipoprotein A-I vascular gene therapy reduces vein-graft atherosclerosis

Autor: Lianxiang Bi, Bradley K. Wacker, Kaushik Komandur, Nicole Sanford, David A. Dichek
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecular Therapy: Methods & Clinical Development, Vol 30, Iss , Pp 558-572 (2023)
Druh dokumentu: article
ISSN: 2329-0501
DOI: 10.1016/j.omtm.2023.08.018
Popis: Coronary artery venous bypass grafts typically fail because of atherosclerosis driven by lipid and macrophage accumulation. Therapy for vein-graft atherosclerosis is limited to statin drugs, which are only modestly effective. We hypothesized that transduction of vein-graft endothelium of fat-fed rabbits with a helper-dependent adenovirus expressing apolipoprotein AI (HDAdApoAI) would reduce lipid and macrophage accumulation. Fat-fed rabbits received bilateral external jugular vein-to-carotid artery interposition grafts. Four weeks later, one graft per rabbit (n = 23 rabbits) was infused with HDAdApoAI and the contralateral graft with HDAdNull. Grafts were harvested 12 weeks later. Paired analyses of grafts were performed, with vein graft cholesterol, intimal lipid, and macrophage content as the primary endpoints. HDAd genomes were detected in all grafts. APOAI mRNA was median 63-fold higher in HDAdApoAI grafts versus HDAdNull grafts (p
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