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


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.
Checchia
Paul A
PA
Center for Critical Illness and Health Engineering and the Departments of Pediatrics and Surgery, Washington University School of Medicine, St. Louis, MO, USA. pchecchia@wustl.edu
Schierding
William
W
Polpitiya
Ashoka
A
Dixon
David
D
Macmillan
Sandy
S
Muenzer
Jared
J
Stromberg
Paul
P
Coopersmith
Craig M
CM
Buchman
Timothy G
TG
Cobb
J Perren
JP
D000367:Age Factors; D000818:Animals; D019317:Evidence-Based Medicine; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium; D020411:Oligonucleotide Array Sequence Analysis; D018805:Sepsis / Q000503:physiopathology*