Cigarette smoke induces rapid changes in gene expression in pulmonary arteries.
The pathogenesis of cigarette smoke-induced pulmonary hypertension is not well characterized. We used RT-PCR to examine gene expression of nitric oxide synthase 2 (NOS-2), nitric oxide synthase 3 (NOS-3), endothelin, and vascular endothelial growth factor (VEGF) and its flk-1 receptor (VEGF-R) in main pulmonary arteries and in intraparenchymal arteries microdissected from alcohol-fixed paraffin blocks. The main pulmonary artery and intraparenchymal vessels responded in a similar fashion, with up-regulation of endothelin, VEGF, and VEGF-R gene expression evident by 2 hours after smoke exposure. Up-regulation of gene expression was still present at 24 hours after exposure, and at this time there was also a small increase in NOS-2. As a comparison, we examined the trachea and microdissected intraparenchymal airways and found up-regulation of endothelin and NOS-2 at 2 hours and additional up-regulation of NOS-3 at 24 hours. These findings suggest that the pulmonary vasculature very rapidly responds to cigarette smoke with up-regulation of mediators that control vascular cell proliferation and vascular constriction. These changes support the idea that pulmonary hypertension in cigarette smokers reflects a direct effect of smoke on the vasculature. The pattern of response in the vessels is distinctly different from that in the airways.
Wright
Joanne L
JL
Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada. jlwright@interchange.ubc.ca
Tai
Hsin
H
Dai
Jin
J
Churg
Andrew
A
D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006976:Hypertension, Pulmonary / Q000209:etiology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011651:Pulmonary Artery / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*
D012906:Smoke