Role of extracellular histones in the cardiomyopathy of sepsis

Kalbitz M, Grailer JJ, Fattahi F, Jajou L, Herron TJ, Campbell KF, Zetoune FS, Bosmann M, Sarma JV, Huber-Lang M, Gebhard F, Loaiza R, Valdivia HH, Jalife J, Russell MW, Ward PA (2015)

Publication Type: Journal article

Publication year: 2015

Journal

The FASEB Journal Federation of American Society of Experimental Biology (FASEB)

Book Volume: 29

Pages Range: 2185-2193

Journal Issue: 5

DOI: 10.1096/fj.14-268730

Abstract

The purpose of this study was to define the relationship in polymicrobial sepsis (in adult male C57BL/6 mice) between heart dysfunction and the appearance in plasma of extracellular histones. Procedures included induction of sepsis by cecal ligation and puncture and measurement of heart function using echocardiogram/Doppler parameters. We assessed the ability of histones to cause disequilibrium in the redox status and intracellular [Ca]i levels in cardiomyocytes (CMs) (from mice and rats). We also studied the ability of histones to disturb both functional and electrical responses of hearts perfused with histones. Main findings revealed that extracellular histones appearing in septic plasma required C5a receptors, polymorphonuclear leukocytes (PMNs), and the Nacht-, LRR-, and PYD-domains-containing protein 3 (NLRP3) inflam-masome. In vitro exposure of CMs to histones caused loss of homeostasis of the redox system and in [Ca +]i,aswellas defects in mitochondrial function. Perfusion of hearts with histones caused electrical and functional dysfunction. Finally, in vivo neutralization of histones in septic mice markedly reduced the parameters of heart dysfunction. Histones caused dysfunction in hearts during polymicrobial sepsis. These events could be attenuated by histone neutralization, suggesting that histones may be targets in the setting of sepsis to reduce cardiac dysfunction.

Involved external institutions

University of Michigan US United States (USA) (US) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE)

How to cite

APA:

Kalbitz, M., Grailer, J.J., Fattahi, F., Jajou, L., Herron, T.J., Campbell, K.F.,... Ward, P.A. (2015). Role of extracellular histones in the cardiomyopathy of sepsis. The FASEB Journal, 29(5), 2185-2193. https://doi.org/10.1096/fj.14-268730

MLA:

Kalbitz, Miriam, et al. "Role of extracellular histones in the cardiomyopathy of sepsis." The FASEB Journal 29.5 (2015): 2185-2193.

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