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Toll-Like Receptor-Mediated Cardiac Injury during Experimental Sepsis
Ina Lackner1, Birte Weber1, Shinjini Chakraborty2
1Department of Traumatology, Hand, Plastic, and Reconstructive Surgery, Center of Surgery, University of Ulm, 89081 Ulm, Germany.
Insights
Sepsis impacts cardiac structure and gap junction proteins, potentially causing heart dysfunction. This study investigated these effects in mice and cell models, revealing key molecular changes.
Area of Science:
- Cardiology
- Molecular Biology
- Immunology
Background:
- Sepsis leads to widespread cardiac dysfunction and high mortality.
- Septic cardiomyopathy arises from complex molecular interactions.
- Understanding sepsis's cardiac effects is crucial for treatment.
Purpose of the Study:
- To investigate the impact of sepsis on cardiac structure proteins.
- To analyze alterations in gap junction and tight junction (TJ) proteins during sepsis.
- To explore the role of LPS and P2X7 in sepsis-induced cardiac changes.
Main Methods:
- Sepsis induced via cecal ligation and puncture in mice.
- Analysis of cardiac protein and mRNA expression.
- HL-1 cells and human iPS cardiomyocytes stimulated with LPS.
- Measurement of reactive oxygen species and troponin I release.
Main Results:
- Polymicrobial sepsis decreased connexin43 and α-actinin protein expression in vivo.
- LPS stimulation increased mRNA expression of connexin43, α-actinin, and desmin in HL-1 cells.
- Troponin I release observed in HL-1 cells upon LPS and nigericin exposure; TJ proteins unaffected in vivo.
Conclusions:
- Sepsis alters cardiac structure and gap junction proteins in mice.
- These changes may contribute to sepsis-induced cardiac dysfunction.
- Further research is needed to elucidate the precise mechanisms.
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.
