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This Article Full Text Full Text (PDF) All Versions of this Article: 286/5/H1775    most recent 00281.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Jones, J. E. Articles by Zhang, Y.-Y. Search for Related Content PubMed PubMed Citation Articles by Jones, J. E. Articles by Zhang, Y.-Y.

Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats

¹Department of Surgery, ²Whitaker Cardiovascular Institute and Evans Department of Medicine, and ³The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118; and ⁴Division of Cardiopulmonary Pathology and Pulmonary and Critical Care Medicine, Department of Pathology and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Submitted 31 March 2003 ; accepted in final form 7 January 2004

5-Lipoxygenase (5-LO) and its downstream leukotriene products have been implicated in the development of pulmonary hypertension. In this study, we examined the effects of 5-LO overexpression in rat lungs on pulmonary hypertension using a recombinant adenovirus expressing 5-LO (Ad5-LO). Transthoracic echocardiography and right heart catheterization data showed that 5-LO overexpression in the lung did not cause pulmonary hypertension in normal rats; however, it markedly accelerated the progression of pulmonary hypertension in rats treated with monocrotaline (MCT). An increase in pulmonary artery pressure occurred earlier in the rats treated with MCT + Ad5-LO (7–10 days) compared with those treated with control vector, MCT + adenovirus expressing green fluorescent protein (AdGFP), or MCT alone (15–18 days). The weight ratio of the right ventricle to left ventricle plus septum was higher in the MCT + Ad5-LO group than that of the MCT + AdGFP or MCT group (0.45 ± 0.08 vs. 0.35 ± 0.03 or 0.33 ± 0.06). Lung tissue histological sections from MCT + Ad5-LO rats exhibited more severe inflammatory cell infiltration and pulmonary vascular muscularization than those from MCT + AdGFP- or MCT-treated rats. Administration of 5-LO inhibitors, zileuton or MK-886, to either MCT- or MCT + Ad5-LO-treated rats prevented the development of pulmonary hypertension. These data suggest that 5-LO plays a critical role in the progression of pulmonary hypertension in rats and that the detrimental effect of 5-LO is manifest only in the setting of pulmonary vascular endothelial cell dysfunction.

inflammation; monocrotaline

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