Transcriptome profiling of murine aortic endothelium with combined deletion for three MEF2 transcription factors: Mef2a, Mef2c and Mef2d

Atherosclerosis predominantly forms in regions of oscillatory shear stress while regions of laminar shear stress are protected. This protection is partly through the endothelium in laminar flow regions expressing an anti-inflammatory and anti-thrombotic gene expression program. Several molecular pathways transmitting these distinct flow patterns to the endothelium have been defined. Our objective is to define the role of the MEF2 family of transcription factors in promoting an atheroprotective endothelium. Endothelial-specific Mef2a -c and -d deficiency results in systemic inflammation, hemorrhage, thrombocytopenia, leukocytosis, and rapid lethality at 11 days post-injection. We collected RNA from the aortic endothelium at day 7 and process for transcriptome analysis in order to understand the phenotype and mechanism. Endothelial-specific, inducible-deletion of Mef2a, Mef2c and Mef2d was mediated by Cdh5-CreERT2 through 5 daily tamoxifen injections in 10 weeks old mice (ACDiEKO). Control animals were tamoxifen injected Cre-negative littermates. Thoracic aortas from these mice were harvest 7 days after the first injection of tamoxifen. Endothelial RNA from individual aortas was isolated by flushing TRIzol through the aortic lumen and processed for Clariom D Mouse assay (formally Mouse Transcriptome Array 1.0) (Affymetrix). Each sample was from a single aorta.