Abstract
BackgroundPulmonary thromboembolism (PTE) is a common diagnosis and a leading cause of cardiovascular morbidity and mortality. A growing literature has associated PE with systemic inflammation, and global hyper-coagulability, which contribute to lung remodeling and clot recurrence. The source and mechanism of inflammation remains unstudied. In humans, inhibition of cholesterol synthesis with statins decreases biomarkers of inflammation. We test the differential effect of pulmonary vascular occlusion during mild and severe pulmonary embolism on the lung transcriptome.MethodsExperimental PE was induced in adult male rats by injection of 25 micron polystyrene microspheres into the jugular vein. The effect of Mild PE, (2-h right ventricular systolic pressure [RVSP] normal, 18-h RVSP 44 mmHg) and Severe PE (2-h RVSP > 50 mmHg; 18-h RVSP 44 mmHg) on lungs was assessed by measuring transcriptome-wide changes in gene expression by DNA microarrays.ResultsSevere PE was associated with a large change in lung gene expression and in the expression of KEGG pathways and other gene functional annotation groups. Mild PE was also associated with a large number of significant changes in gene expression and in the expression of KEGG pathways and gene functional annotation groups, even after only 2 h of PE. Up-regulated pathways included increased adipocytokine, chemokine and cytokine signaling as well as cholesterol synthesis.ConclusionsMild PE without acute pulmonary hypertension (PH) increased lung gene expression of inflammatory pathways, including increased cholesterol synthesis. These data indicate that even mild persistent pulmonary vascular occlusion is capable of inciting an inflammatory response from the lung. These data imply the detrimental effect of unresolved pulmonary obstruction from PE.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0405-9) contains supplementary material, which is available to authorized users.
Highlights
Pulmonary thromboembolism (PTE) is a common diagnosis and a leading cause of cardiovascular morbidity and mortality
The three 2-h groups were closely associated, as were the 18-h Mild Pulmonary embolism (PE) and 18-h Severe PE groups while the 18-h vehicle clustered with the 2-h vehicle
Comparison of the Mild PE and Severe PE treatment groups at the same times revealed that the 18 h Severe PE group had 1.84-fold more altered probesets than the 18 h Mild PE group (4048 verses 2195), while the Severe PE group had fewer altered probesets at 2 h than the Mild PE group (177 verses 496)
Summary
Pulmonary thromboembolism (PTE) is a common diagnosis and a leading cause of cardiovascular morbidity and mortality. A growing literature has associated PE with systemic inflammation, and global hyper-coagulability, which contribute to lung remodeling and clot recurrence. The most common form of PE is pulmonary thromboembolism (PTE), which results when blood clots, often formed in the deep vasculature of the legs, detach and enter the venous circulation. Increased lung inflammation has been implicated as a mechanism of reduced angiogenesis, and for increased hyper-coagulability, leading to recurrent PE [10, 12, 13]. With deprivation of blood flow to the lung triggers a brisk inflammatory response [18]
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