Significant correlation between endothelial nitric oxide synthase (eNOS) expression and alveolar repair in elastase-induced rat pulmonary emphysema.
OBJECTIVE
Angiogenic factors, such as endothelial nitric oxide synthase (eNOS), are thought to play an important role in the repair of pulmonary emphysema (PE); yet, the correlation of the factors involved has not been investigated. We conducted this study to clarify the positive correlation between eNOS expression and alveolar repair in PE recovery.


METHODS
We used elastase to induce PE in rats, which were divided into Groups A (Control), B (G-CSF), C (PE) and D (PE + G-CSF). G-CSF was injected for 12 days, 4 weeks after which the alveolar walls, arterioles, and angiogenic factors including eNOS were examined histopathologically and by western blotting.


RESULTS
In comparing Groups A, B, C, and D, the alveolar density was 2.4 ± 0.2, 2.4 ± 0.1, 1.8 ± 0.1, 2.5 ± 0.1 per 100 μm(2), respectively (C vs. others; p < 0.00001) and the number of arterioles was 4.5 ± 1.0, 5.6 ± 0.6, 3.2 ± 0.5, 5.5 ± 0.7/mm(2), respectively (C vs. others; p < 0.05). Immunohistochemical staining (IHC) revealed different eNOS expression in Group D versus Group C (p < 0.0001) and western blotting revealed different eNOS, VEGF, and FLT-1 expression in Group D versus Group C (p < 0.01, p < 0.05, p < 0.001), reflecting the contribution of angiogenesis to PE repair. eNOS showed a significantly positive correlation to alveolar density and arteriole repair.


CONCLUSIONS
Alveolar repair was correlated positively with eNOS expression by vascular regeneration in elastase-induced rat PE.
Department of Thoracic Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. hiromi396@aol.com
Hiromichi
H
Ito
Shonosuke
S
Matsushita
Shigemi
S
Ishikawa
Yukinobu
Y
Goto
Mitsuaki
M
Sakai
Masataka
M
Onizuka
Yukio
Y
Sato
Yuzuru
Y
Sakakibara
D000818:Animals; D001160:Arterioles / Q000201:enzymology; D015153:Blotting, Western; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000098:blood supply* / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function
D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat