Increased Eicosanoid Levels in the Sugen/Chronic Hypoxia Model of Severe Pulmonary Hypertension
Year: 2015
Type: article
Abstract: Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established.
Source: PLoS ONE
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1140289417, G1160139270, The Role of Ceramide Kinase in Eicosanoid Synthesis, G2445319642, G2524726931, AB SCIEX 5500 QTRAP Mass Spectrometer for Lipidomics and Metabolomics Research, The functional role of the cPLA2alpha/C1P interaction in sepsis resolution, G46402933, G4670433464, G4799061886, G5514841323, G5770983250, G6295537351, Signaling in Tissue Injury and Repair, Regulation of caspase 9 RNA splicing in NSCLC cancer, G6822895880, CONSTRUCTION OF SIGNALLING FACILITY, G7483374307, G8173979607, G9000186613, Massey Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2029139678