Acute pulmonary embolism (PE) is the third leading cause of cardiovascular death in the United States. Moderate to severe PE can cause pulmonary arterial hypertension (PH) with resultant right ventricular (RV) heart damage. The mechanisms leading to RV failure after PE are not well defined, although it is becoming clear that PH-induced inflammatory responses are involved. We have previously demonstrated profound neutrophil-mediated inflammation and RV dysfunction during PE which was associated with increased expression of several chemokine genes. However, a complete assessment of transcriptional changes in RVs during PE is still lacking. We have now used DNA microarrays to assess the alterations in gene expression in right ventricular tissue during acute PE/PH in rats. Key results were confirmed with Real-Time RT PCR. Nine CC-chemokine genes (CCL-2, 3, 4, 6, 7, 9, 17, 20, 27), 5 CXC-chemokine genes (CXCL-1, 2, 9, 10, 16) and the receptors CCR1 and CXCR4 were up-regulated after 18 hours of moderate PE while one C-chemokine (XCL-1) and one CXC-chemokine (CXCL-12) were down-regulated. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses indicated increased expression of many inflammatory genes. There was also a major shift in the expression of components of metabolic pathways, including down-regulation of fatty acid transporters and oxidative enzymes, a change in glucose transporters and up-regulation of stretch sensing and hypoxia-inducible transcription factors. This pattern suggests an extensive shift in cardiac physiology favoring the expression of the "fetal gene program".