Baculoviral vector encoding mutant HIF-1alfa as a possible treatment for peripheral arterial disease

CARLOS S. GIMÉNEZ; SIMONIN JA; CROTTOGINI A; NUÑEZ PEDROZO CN; CUNIBERTI L; CASTILLO MG; BELAICH MN; OLEA FD

Mar del Plata

Congreso; Reunión Anual SAIC SAFE SAB SAP 2019; 2019

Introduction: Peripheral artery disease (PAD) is an ailment characterized by decreased arterial blood flow to the lower limbs. Given the lack of effective treatments, angio-arteriogenesis has been proposed. We hypothesized that the administration of a baculovirus encoding mutant HIF-1α (Bv.mHIF-1α) would induce collateral vessels neoformation in the ischemic limb.Materials and methods: A. In vitro studies: 1) Transgene expression: Skeletal myoblast (Skm) isolated from rabbit adductor muscle were transduced with Bv.mHIF-1 at MOI=100, and HIF-1α expression was evaluated by RT-qPCR and western blot. 2) Angiogenic potential of transduced cells: the tubulogenesis assay was performed with supernatants of SkM and SkM-mHIF-1α cultures. B. In vivo studies: 12 rabbits underwent sterile excision of the femoral artery of the left posterior limb. Seven days later, rabbits were randomized to receive in the ischemic muscle 10 injections containing 109 copies of the Bv.mHIF-1α vector (treated group, n=6) or 109 copies of Bv.null (control group, n=6). Two weeks post-treatment digital angiography was performed in both posterior limbs.Results: HIF-1α mRNA levels in SkM-mHIF-1α cells was 1000-fold higher than in non-transduced cells (p