title: Differential effect of mild and severe pulmonary embolism on the rat lung transcriptome.
abstract: 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 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.
  
  
  
  Experimental 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.
  
  
  
  Severe 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.
  
  
  
  Mild 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.
authors.affiliation: Department of Math and Sciences, Gaston College, Dallas, NC, 28014, USA.
authors.forename: John
authors.initials: J
authors.lastname: Zagorski
authors.affiliation: Department of Emergency Medicine and Department of Cellular and Integrative Physiology, Indiana University Medical School, 720 Eskanazi Avenue, Indianapolis, IN, 46202, USA. jefkline@iu.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kline
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008168:Lung / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011014:Pneumonia / Q000235:genetics* / Q000378:metabolism; D011655:Pulmonary Embolism / Q000235:genetics* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors; D059467:Transcriptome
keywords: DAVID; Fibrinolysis; GeneSifter; Inflammation; Lung; Microarray; Pulmonary hypertension; Thrombolysis