RGD Reference Report - Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats. - Rat Genome Database

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

Authors: Jones, JE  Walker, JL  Song, Y  Weiss, N  Cardoso, WV  Tuder, RM  Loscalzo, J  Zhang, YY 
Citation: Jones JE, etal., Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1775-84. Epub 2004 Jan 15.
RGD ID: 4890418
Pubmed: PMID:14726295   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.00281.2003   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pulmonary hypertension  ISOAlox5 (Rattus norvegicus)4890418; 4890418 RGD 
pulmonary hypertension  IMP 4890418 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Alox5  (arachidonate 5-lipoxygenase)

Genes (Mus musculus)
Alox5  (arachidonate 5-lipoxygenase)

Genes (Homo sapiens)
ALOX5  (arachidonate 5-lipoxygenase)


Additional Information