Myocardial transcriptional profiles in a murine model of sepsis: evidence for the importance of age.

Abstract

BACKGROUND:

Age influences outcome of sepsis and septic shock. The mechanism of this age-dependent vulnerability to sepsis remains largely unknown. Because much of the mortality and morbidity associated with sepsis and septic shock is the result of severe derangements in the cardiovascular system, it is possible that the myocardium responds to injury in a developmentally influenced manner. We hypothesized that analysis of cardiac RNA expression profiles may differentiate between the myocardial response to sepsis in young and old mice.

METHODS AND RESULTS:

Sixteen FVB/N male mice were stratified based on age. Young animals were 6 wks old, correlating to 4 to 6 human years, and aged animals were 20 months old correlating to 70 to 80 human years. Animals underwent either cecal ligation and puncture to produce polymicrobial sepsis or a sham operation. Both ventricles were excised after kill at 24 hrs. There were 53 genes that differed in RNA abundance between the four groups (false discovery rate of 0.005, p < 0.00001). Additionally, four genes were associated with an age-dependent response to sepsis: CYP2B2 (cytochrome P450, family 2, subfamily B, polypeptide 6), VGLL2 (vestigial like 2), and PAH (phenylalanine hydroxylase). The fourth gene is an expressed sequence tag, the function of which is related to the cytochrome P450 family. These genes play roles in phenylalanine, tyrosine, tryptophan, and fatty acid metabolism.

CONCLUSIONS:

This report describes the transcriptional response of the heart to sepsis. In addition, our findings suggest that these differences are in part age-dependent and serve as hypothesis generation.

• Authors: Paul A Checchia, William Schierding, Ashoka Polpitiya, David Dixon, Sandy Macmillan, Jared Muenzer, Paul Stromberg, Craig M Coopersmith, Timothy G Buchman, J Perren Cobb
• Journal: Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies (Pediatr Crit Care Med) Vol. 9 Issue 5 Pg. 530-5 (Sep 2008) ISSN: 1529-7535 [Print] United States
• PMID: 18679145 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Age Factors
• Animals
• Evidence-Based Medicine
• Mice
• Mice, Inbred Strains
• Myocardium
• Oligonucleotide Array Sequence Analysis
• Sepsis (physiopathology)