Sepsis-induced myocardial depression is associated with transcriptional changes in energy metabolism and contractile related genes: a physiological and gene expression-based approach
Abstract
Increased nitric oxide production and altered mitochondrial function have been implicated in sepsis-induced cardiac dysfunction. The molecular mechanisms underlying myocardial depression in sepsis and the contribution of nitric oxide in this process however, are incompletely understood. To assess the transcriptional profile associated with sepsis-induced myocardial depression in a clinically relevant mouse model, and specifically test the hypothesis that critical transcriptional changes are inducible nitric oxide synthase-dependent. Laboratory investigation. University affiliated research laboratory. C57/BL6 wild type and congenic B6 129P2-Nos2tm1Lau/J (iNOS) mice. Assessment of myocardial function after 48 hrs of induction of polymicrobial sepsis by caecal ligation and perforation. We compared the myocardial transcriptional profile in C57/BL6 wild type mice and congenic B6 129P2-Nos2tm1Lau/J litter mates after 48 hrs of polymicrobial sepsis induced by caecal ligation and perforation. Profiling of 22,690 expressed sequence tags by gene set enrichment analysis demonstrated that inducible nitric oxide synthase -/- failed to down regulate critical bioenergy and metabolism related genes including the gene for peroxisome proliferato...Continue Reading
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