Endotoxin and cytokines alter contractile protein expression in cardiac myocytes in vivo

Release of bacterial endotoxin and cytokines induce cardiac failure during sepsis. We investigated the direct effects of E. coli endotoxin (lipopolysa ccharide, LPS) and cytokines induced by LPS on the cardiac myocyte gene pro gram. For in vivo-experiments adult Wistar rats were given 600 mug/day LPS i.v. for 24 h or 7 days. In addition. cultured adult rat cardiac myocytes w ere treated with LPS, interleukin-l beta (IL-1 beta), tumour necrosis facto r-alpha (TNF alpha), interferon-gamma (IFN gamma) or IL-6 for 24 h. mRNA ex pression was evaluated for cardiac-alpha -actin (cAct), skeletal-alpha -act in (skAct), beta- and alpha -myosin heavy chain (MHC). LPS induced beta MHC -mRNA 3.6-fold and repressed alpha MHC 2.7-fold and cAct 2.5-fold after 24 h in vivo. Up-regulation of beta MHC (3-fold) and repression of cAct (2.5-f old) were still observed after 7 days LPS infusion. whereas alpha MHC-mRNA levels had returned to normal. At the protein level. increased expression o f beta MHC by LPS treatment occurred already after 24 h and was maintained thereafter. LPS had no influence on skAct-mRNA. Similar changes in contract ile protein mRNA expression were observed in LPS-treated cardiomyocytes in culture, whereas the tested cytokines either activated (IL-1 beta, IFN gamm a) or repressed (TNF alpha, IL-6) both MHC-isoforms and cAct. In conclusion . LPS and proinflammatory cytokines induce changes in contractile protein e xpression that may contribute to the acute heart failure observed during en dotoxaemia.