%0 Journal Article %1 Wondergem2014 %A Wondergem, R %A Graves, B %A Ozment, T R %A Williams, D L %D 2014 %J Shock %K Escherichia_coli agonist calcium_cell_level calcium_signaling cardiac_muscle_cell endotoxin flow_cytometry heart_failure human implantable_cardioverter_defibrillator lipopolysaccharide myopathy oscillation pacemaker peptide pluripotent_stem_cell society stimulation toll_like_receptor_2 toll_like_receptor_4 %R 10.1097/SHK.0000000000000184 %T Lipopolysaccharides directly increase calcium oscillations and intracellular calcium in human cardiomyocytes %X Lipopolysaccharides (LPS) are involved in endotoxin-mediated heart failure and chronic cardiac myopathies. We have shown previously that lipopolysaccharides (LPS) directly affect murine-derived HL-1 cardiac myocyte function via TLR-4 by inhibiting Ca2+ oscillations, by decreasing intracellular Ca2+ concentration, Ca2+i, and by impairing pacemaker Bfunny current, If, (Wondergem et al. Am. J. Physiol. Cell Physiol. 299:C665-71, 2010). Here we report LPS effects on human, induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (iCellA Cardiomyocytes). In marked contrast to the inhibitory effects of LPS on HL-1 cells, LPS (S. enteriditis or E. coli) in a dose-dependent manner (0.01- 1.0 2g/ml) increased the rate of Ca2+ oscillations and the Ca2+i in iCell Cardiomyocytes. Ca2+-free external solution abolished this stimulation by LPS. Ultra-pure LPS (E. coli), which is considered a TLR-4 specific agonist, exerted identical effects as the impure LPS. Prior addition of the monoclonalantibody blocking peptide, MAb hTLR4, attenuated the effect of ultra-pure LPS. Pam3Csk, a TLR-2 agonist, had no effect on Ca2+ oscillations or Ca2+i. iCell Cardiomyocytes also expressed TLR-4 as determined by flow cytometry. We conclude that LPS, acutely applied to human iCell Cardiomyocytes, results in TLR-4-dependent increases in Ca2+ oscillations and Ca2+i, which are consistent with a hyperdynamic response. This is in marked contrast to the hypodynamic response that we reported previously for acute effects of LPS on murine cardiomyocytes.

@article{Wondergem2014, abstract = {Lipopolysaccharides (LPS) are involved in endotoxin-mediated heart failure and chronic cardiac myopathies. We have shown previously that lipopolysaccharides (LPS) directly affect murine-derived HL-1 cardiac myocyte function via TLR-4 by inhibiting Ca2+ oscillations, by decreasing intracellular Ca2+ concentration, [Ca2+]i, and by impairing pacemaker Bfunny[ current, If, (Wondergem et al. Am. J. Physiol. Cell Physiol. 299:C665-71, 2010). Here we report LPS effects on human, induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (iCellA Cardiomyocytes). In marked contrast to the inhibitory effects of LPS on HL-1 cells, LPS (S. enteriditis or E. coli) in a dose-dependent manner (0.01- 1.0 2g/ml) increased the rate of Ca2+ oscillations and the [Ca2+]i in iCell Cardiomyocytes. Ca2+-free external solution abolished this stimulation by LPS. Ultra-pure LPS (E. coli), which is considered a TLR-4 specific agonist, exerted identical effects as the impure LPS. Prior addition of the monoclonalantibody blocking peptide, MAb hTLR4, attenuated the effect of ultra-pure LPS. Pam3Csk, a TLR-2 agonist, had no effect on Ca2+ oscillations or [Ca2+]i. iCell Cardiomyocytes also expressed TLR-4 as determined by flow cytometry. We conclude that LPS, acutely applied to human iCell Cardiomyocytes, results in TLR-4-dependent increases in Ca2+ oscillations and [Ca2+]i, which are consistent with a hyperdynamic response. This is in marked contrast to the hypodynamic response that we reported previously for acute effects of LPS on murine cardiomyocytes.}, added-at = {2019-06-18T22:58:43.000+0200}, author = {Wondergem, R and Graves, B and Ozment, T R and Williams, D L}, biburl = {https://www.bibsonomy.org/bibtex/2cf558fd04a75b0313c9426df2399e31a/fcdi}, doi = {10.1097/SHK.0000000000000184}, interhash = {9d4b6ee014b3f85810437fd1f4e163b3}, intrahash = {cf558fd04a75b0313c9426df2399e31a}, issn = {1073-2322}, journal = {Shock}, keywords = {Escherichia_coli agonist calcium_cell_level calcium_signaling cardiac_muscle_cell endotoxin flow_cytometry heart_failure human implantable_cardioverter_defibrillator lipopolysaccharide myopathy oscillation pacemaker peptide pluripotent_stem_cell society stimulation toll_like_receptor_2 toll_like_receptor_4}, timestamp = {2019-06-18T22:58:43.000+0200}, title = {{Lipopolysaccharides directly increase calcium oscillations and intracellular calcium in human cardiomyocytes}}, year = 2014 }