Comparing genomic changes in mice strains demonstrating physiologic differences with pathologic insults is a novel approach to elucidate potential mechanisms. Our hypothesis was that murine strains exhibit different cardiac/genomic responses to specific pathogens.
The end-systolic pressure–volume relationship (ESPVR) and end-diastolic pressure–volume relationship (EDPVR) cardiac performance was compared in B6, C57 and FVB mice (pressure–volume loops, Millar catheter; isoflurane anesthesia) 4 hours after zymosan (ZYM) or endotoxin (LPS) intraperitoneally. Gene expression profiles unique to mouse strain/baseline/treatment were created using two-way ANOVA/two-fold filtering.
ESPVR improved in B6/C57 mice after ZYM (Figure 1). Diastolic compromise (Figure 2) occurred in FVB mice following ZYM but in B6 mice after LPS. Genomic analyses within strains revealed pathogen-specific differences: for example, ZYM-treated FVB mice (diastolic impairment) demonstrated downregulation of key cell cycle, vascular endothelial growth factor, L-type calcium channel genes, with upregulation of T-cell receptor and the src-family kinase (exaggerated inflammatory response).
Comparative genomic analyses provide new insights into septic cardiac pathophysiology.
Supported in part by the National Heart, Lung and Blood Institute (Patterson), and the Intensive Care Society (Ackland).