Sequential and timely transfection of hepatocyte growth factor and monocyte chemotactic protein-1 ameliorates hyperkinetic pulmonary artery hypertension in rabbits.
OBJECTIVE
To investigate the effect of sequential and timely transfection of the recombinant human hepatocyte growth factor (hHGF) gene and human monocyte chemotactic protein-1 (hMCP-1) gene on hyperkinetic pulmonary artery hypertension in a rabbit model.


METHODS
The rabbits with pulmonary artery hypertension were randomly separated into 5 groups: control; hHGF; hMCP-1; hHGF/hMCP-1 simultaneous transfection; and hHGF/hMCP-1 sequential, timely transfection. Two weeks after the transfection, real-time polymerase chain reaction and immunohistochemistry examination were used to detect the expression of hHGF and hMCP-1. Four weeks later, the hemodynamic parameters were measured, and immunohistochemical and immunofluorescence staining were performed, to investigate microvascular density and arterialization.


RESULTS
The final adenovirus coding with enhanced green fluorescent protein-hMCP-1 virus was 3 × 10(10) plaque-forming units/mL, and the purity of adenovirus coding with hHGF was 1.31. Three days after the transfection, enhance green fluorescent protein hMCP-1 green fluorescence was detected in the lung tissues and increased to its peak point in 1 week. Two weeks later, hHGF and hMCP-1 were expressed in all transfection groups. By the end of 4 weeks, the mean pulmonary artery pressure in the hHGF/hMCP-1 sequential and timely transfection group was lower than that in the other groups. Confirmed by immunohistochemical and immunofluorescence staining, the microvascular and arteriolar density in the lung tissues of the sequential and timely hHGF/hMCP-1 transfection group were higher than that in the other groups.


CONCLUSIONS
Expression of hHGF and hMCP-1 were found in rabbit lung after gene transfection via an airway approach. By increasing the pulmonary microvascular density and promoting arterializations, sequential and timely hHGF/hMCP-1 transfection ameliorates the shunt flow-induced pulmonary artery hypertension.
Department of Cardiothoracic Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
Yiqian
Y
Zhang
Department of Rheumatology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
Fang
F
Zhang
Department of Cardiothoracic Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
Xiaoyu
X
Wang
Department of Cardiothoracic Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
Yue
Y
Xie
Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Junjie
J
Du
Department of Cardiothoracic Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
Peng
P
Lu
Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China. Electronic address: 18052268137@163.com.
Wei
W
Wang
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D062186:Arterial Pressure; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D057809:HEK293 Cells; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018919:Neovascularization, Physiologic; D011651:Pulmonary Artery / Q000503:physiopathology*; D011652:Pulmonary Circulation; D011817:Rabbits; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection
C111835:CCL2 protein, human; D018932:Chemokine CCL2; C066855:HGF protein, human; D017228:Hepatocyte Growth Factor
angiogenesis; hepatocyte growth factor (HGF); microvascular arterialization; monocyte chemotactic protein-1 (hMCP-1); pulmonary artery hypertension (PAH)