Abstract 18751: Inhalable Delivery of AAV-based Mrp4/abcc4 Silencing Rna Attenuates Monocrotaline-induced Pulmonary Hypertension

The ATP-binding cassette transporter MRP4 (encoded by ABCC4) functions as a plasma membrane efflux pump to extrude cyclic nucleotides from various cell types. MRP4 regulates membrane cyclic nucleotides concentrations in arterial cells including smooth muscle cells (SMCs). In previous experiments, we have shown that MRP4 silencing inhibits SMCs proliferation in vitro. Concordantly, MRP4/ABCC4 deficient mice display a reduction in SMCs proliferation and a prevention of pulmonary hypertension in response to hypoxia. We here aimed to study gene transfer of a MRP4/ABCC4 silencing RNA via intratracheal delivery (using a MicroSprayer® Aerosolizer) of aerosolized adeno-associated virus 1 (AAV1.shMRP4 or AAV1.control) in a monocrotaline-induced model of pulmonary hypertension in rats. Gene transfer was performed at the time of monocrotaline administration and the effect on the development of pulmonary vascular remodeling was assessed thirty-five days later. The efficiency of this approach to transduce the lung vas...