TY - JOUR
T1 - Myocardial transcriptional profiles in a murine model of sepsis
T2 - Evidence for the importance of age
AU - Checchia, Paul A.
AU - Schierding, William
AU - Polpitiya, Ashoka
AU - Dixon, David
AU - MacMillan, Sandy
AU - Muenzer, Jared
AU - Stromberg, Paul
AU - Coopersmith, Craig M.
AU - Buchman, Timothy G.
AU - Cobb, J. Perren
PY - 2008/9
Y1 - 2008/9
N2 - 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.
AB - 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.
KW - Aging
KW - Genetics
KW - Heart failure
KW - Inflammation
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=60849101889&partnerID=8YFLogxK
U2 - 10.1097/PCC.0b013e3181849a2f
DO - 10.1097/PCC.0b013e3181849a2f
M3 - Article
C2 - 18679145
AN - SCOPUS:60849101889
SN - 1529-7535
VL - 9
SP - 530
EP - 535
JO - Pediatric Critical Care Medicine
JF - Pediatric Critical Care Medicine
IS - 5
ER -