Co-translational profiling in the cardiac endothelium in response to LPS-induced inflammation in female mice in vivo: a proof-of-concept approach

). To perturb endothelial function, female mice were injected with E. coli lipopolysaccharide (LPS) (6 mg/Kg, i.p., 12 h). Hearts were homogenized, with ~ 10% used for input RNA-Seq and proteomics controls, and the remainder for IP of ribosome-bound polyadenylated mRNA and proteins. Endothelial cell transcripts (pecam1, cdh5) were enriched > 5-fold, while markers characteristic of other cell types were significantly depleted (< 0.05 q-value). We aligned transcriptomic and proteomic datasets (> 1250 overlapping terms) to identify pathways associated with concordant and discordant co-translational regulation. LPS was identified as the upstream regulator of the co-translational dataset that was concordantly regulated. Upregulated mRNAs but not proteins related to glycolysis were discordantly regulated. These findings validate our proof-of-concept multi-omics approach as a predictive platform for identifying disease-relevant pathways regulated at the co-translational level in vivo.