AAV delivery of tumor necrosis factor-α short hairpin RNA attenuates cold-induced pulmonary hypertension and pulmonary arterial remodeling.

ABSTRACT: Cold temperatures are associated with increased mortality and morbidity of cardiovascular and pulmonary disease. Cold exposure causes lung inflammation, pulmonary hypertension (PH), and right ventricle hypertrophy, but there is no effective therapy because of unknown mechanism. Here, we investigated whether RNA interference silencing of tumor necrosis factor (TNF)-α decreases cold-induced macrophage infiltration, PH, and pulmonary arterial (PA) remodeling. We found for the first time that continuous cold exposure (5.0°C) increased TNF-α expression and macrophage infiltration in the lungs and PAs right before elevation of right ventricle systolic pressure. The in vivo RNA interference silencing of TNF-α was achieved by intravenous delivery of recombinant AAV-2 carrying TNF-α short hairpin s

SUBMITTER: Crosswhite P 

PROVIDER: S-EPMC4192064 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature