Abstract

divided into four subgroups: Group 1: received s.c. injection of phosphate buffered saline; Group 2: received s.c. injection of MCT (MCT alone); Group 3: received injection of MCT followed by i.v. transfusion of rat PAECs transduced with empty adenoviral vector (Null-EC); and Group 4: received injection of MCT followed by i.v. transfusion of rat PAECs overexpressing IL8RA and RB (IL8RA/RB-EC, total 0.5x10 cells/rat). Two days or 4 wks after MCT treatment, eNOS, iNOS, IL-8 (Cinc-2b in rat) and MCP-1 expression and neutrophil and macrophage infiltration in pulmonary arterioles and alveoli, as well as pulmonary arterial flow pattern and arteriole hypertrophy were measured by histological, immunohistochemical staining and echocardiography, respectively. Results: Compared to the MCT alone and MCT-Null-EC groups, transfusion of IL8RA/RB-ECs significantly decreased MCT-induced neutrophil infiltration and pro-inflammatory mediator expression in pulmonary arterioles and alveoli, reduced pulmonary vascular and RV hypertrophy and remodeling. Conclusion: These provocative findings suggest that targeted delivery of PAECs overexpressing IL8RA and IL8RB is effective in repairing injured pulmonary vasculature. Targeted delivery of PAECs to injured lungs provides a novel strategy for the treatment of pulmonary vascular injury in humans.

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