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Expression of 15-Lipoxygenase and Evidence for Apoptosis in the Lungs From Patients With COPD^*

^* From the Pulmonary Hypertension Center, Department of Medicine (Drs. Kasahara and Voelkel) and Department of Pathology (Drs. Tuder and Cool), University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Yasunori Kashahara, MD, Division of Pulmonary Science and Critical Care Medicine, University of Colorado Health Sciences Center, 4200 E. 9th Ave, Denver, CO 80262

	Introduction

TOP Introduction

 
Abbreviations: KDR = kinase insert domain-containing receptor; VEGF = vascular endothelial growth factor

There is a loss of alveolar structures and endothelial cells in emphysema. We hypothesize that the disappearance of lung alveoli resulting in emphysema may occur by apoptosis following decreased expression or activity of lung vascular endothelial growth factor (VEGF) or its receptor, kinase insert domain-containing receptor(KDR). To examine this hypothesis, we carried out the TUNEL technique in lung samples obtained from 6 patients with emphysema and 11 normal control subjects (7 nonsmokers and 4 smokers). We found an increased number of TUNEL-positive cells/nucleic acids in alveolar septum in emphysema when compared with normal lungs. The cell death events were not different between healthy nonsmokers and nonemphysema smokers. Double staining with TUNEL and cytokeratin or factor VIII-related antigen confirmed endothelial cell and epithelial cell death in emphysema lungs. Western blot analysis for KDR of whole lung protein extracts showed that KDR protein expression was significantly reduced in emphysema lungs. In situ hybridization revealed a focally decreased expression of VEGF and KDR messenger RNA in emphysema lungs. Using immunohistochemistry, we localized and semiquantitatively estimated the abundance of 15-lipoxygenase in lungs obtained from 6 patients with emphysema, 6 normal control subjects, and 7 patients with severe pulmonary hypertension. Expression of 15-lipoxygenase in pulmonary arteries in emphysema was less intense than in severe pulmonary hypertension. We conclude that cell death events occur in emphysema, and that VEGF and its receptor KDR are decreased in emphysema lungs. We speculate that emphysema may occur by apoptosis following decreased expression or activity of lung VEGF or its receptor KDR.

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This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Kasahara, Y. Articles by Voelkel, N. F. Search for Related Content PubMed PubMed Citation Articles by Kasahara, Y. Articles by Voelkel, N. F.