PMID- 12379773 OWN - NLM STAT- MEDLINE DCOM- 20021119 LR - 20230216 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 82 IP - 10 DP - 2002 Oct TI - Cigarette smoke induces rapid changes in gene expression in pulmonary arteries. PG - 1391-8 AB - 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. FAU - Wright, Joanne L AU - Wright JL AD - Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada. jlwright@interchange.ubc.ca FAU - Tai, Hsin AU - Tai H FAU - Dai, Jin AU - Dai J FAU - Churg, Andrew AU - Churg A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Smoke) SB - IM MH - Animals MH - Disease Models, Animal MH - *Gene Expression Regulation MH - Hypertension, Pulmonary/*etiology MH - Muscle, Smooth, Vascular/pathology MH - Pulmonary Artery/*pathology MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Smoke/*adverse effects MH - Smoking/*adverse effects EDAT- 2002/10/16 04:00 MHDA- 2002/11/26 04:00 CRDT- 2002/10/16 04:00 PHST- 2002/10/16 04:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/10/16 04:00 [entrez] AID - S0023-6837(22)03650-9 [pii] AID - 10.1097/01.lab.0000032806.45023.08 [doi] PST - ppublish SO - Lab Invest. 2002 Oct;82(10):1391-8. doi: 10.1097/01.lab.0000032806.45023.08.