Abstract
Sepsis is associated with global cardiac dysfunction and with high mortality rate. The development of septic cardiomyopathy is due to complex interactions of damage-associated molecular patters, cytokines, and complement activation products. The aim of this study was to define the effects of sepsis on cardiac structure, gap junction, and tight junction (TJ) proteins. Sepsis was induced by cecal ligation and puncture in male C57BL/6 mice. After a period of 24 h, the expression of cardiac structure, gap junction, and TJ proteins was determined. Murine HL-1 cells were stimulated with LPS, and mRNA expression of cardiac structure and gap junction proteins, intracellular reactive oxygen species, and troponin I release was analyzed. Furthermore, pyrogenic receptor subtype 7 (P2X7) expression and troponin I release of human cardiomyocytes (iPS) were determined after LPS exposure. In vivo, protein expression of connexin43 and α-actinin was decreased after the onset of polymicrobial sepsis, whereas in HL-1 cells, mRNA expression of connexin43, α-actinin, and desmin was increased in the presence of LPS. Expression of TJ proteins was not affected in vivo during sepsis. Although the presence of LPS and nigericin resulted in a significant troponin I release from HL-1 cells. Sepsis affected cardiac structure and gap junction proteins in mice, potentially contributing to compromised cardiac function.
Highlights
Severe sepsis is associated with a high lethality rate, cardiac dysfunction, and heart failure in rodents as well as in humans [1, 2]
In this study we investigated the effects of septic conditions on cardiac structure, gap junction, and tight junction proteins
In order to determine the inflammatory condition during CLP sepsis in vivo, the expression of the complement factor 3a receptor (C3aR) as well as the expression of interleukin- (IL-) 1β was determined in the left ventricles by microscopy
Summary
Severe sepsis is associated with a high lethality rate, cardiac dysfunction, and heart failure in rodents as well as in humans [1, 2]. Cardiac output, LV stroke volume, and LV ejection fraction decreased in mice, which reflect the cardiodepressive effects of sepsis [5]. This cardiac dysfunction is called cardiomyopathy of sepsis [6]. Patients suffering from septic cardiomyopathy showed enhanced plasma levels of cardiac troponin (cTn), correlating with an increased mortality rate [8, 9]. Enhanced ROS was associated with cardiac remodelling, reduced LV function, and contractile dysfunction [16, 17]. By altering and disturbing their action potentials, C5a induced defects in CM contractility [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
