Experimental blunt chest trauma-induced myocardial inflammation and alteration of gap-junction protein connexin 43

Kalbitz, Miriam; Amann, Elisa Maria; Bosch, Belinda; Palmer, Annette; Schultze, Anke; Preßmar, Jochen; Weber, Birte; Wepler, Martin; Gebhard, Florian; Schrezenmeier, Hubert; Brenner, Rolf E.; Huber‐Lang, Markus

doi:10.1371/journal.pone.0187270

Cited by 29 publications

(34 citation statements)

References 48 publications

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“…An increased amount of deposited C3 cleavage products C3b/iC3b/C3c induces the second inflammatory phase after trauma, resulting in cardiac failure and death (52,53). In the present study, the expression of C5aR1 was slightly decreased in the lumen of the left ventricle after trauma in both polytrauma groups, which was also described previously after 72 h in an experimental polytrauma model in pigs and after 24 h in an experimental blunt chest trauma model in rats (54,55). The decreased expression of C5aR1 after trauma was associated with internalization of the receptor, triggered by C5a, which was further associated with CMs dysfunction and compromised cardiac function (25,56).…”

Section: Discussionsupporting

confidence: 88%

Complement Activation and Organ Damage After Trauma—Differential Immune Response Based on Surgical Treatment Strategy

et al. 2020

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Background: The complement system is part of the innate immunity, is activated immediately after trauma and is associated with adult respiratory distress syndrome, acute lung injury, multiple organ failure, and with death of multiply injured patients. The aim of the study was to investigate the complement activation in multiply injured pigs as well as its effects on the heart in vivo and in vitro. Moreover, the impact of reamed vs. non-reamed intramedullary nailing was examined with regard to the complement activation after multiple trauma in pigs. Materials and Methods: Male pigs received multiple trauma, followed by femoral nailing with/without prior conventional reaming. Systemic complement hemolytic activity (CH-50 and AH-50) as well as the local cardiac expression of C3a receptor, C5a receptors1/2, and the deposition of the fragments C3b/iC3b/C3c was determined in vivo after trauma. Human cardiomyocytes were exposed to C3a or C5a and analyzed regarding calcium signaling and mitochondrial respiration. Results: Systemic complement activation increased within 6 h after trauma and was mediated via the classical and the alternative pathway. Furthermore, complement activation correlated with invasiveness of fracture treatment. The expression of receptors for complement activation were altered locally in vivo in left ventricles. C3a and C5a acted detrimentally on human cardiomyocytes by affecting their functionality and their mitochondrial respiration in vitro. Conclusion: After multiple trauma, an early activation of the complement system is triggered, affecting the heart in vivo as well as in vitro, leading to complement-induced Lackner et al. Complement Activation Induces Cardiac Dysfunction cardiac dysfunction. The intensity of complement activation after multiple trauma might correlate with the invasiveness of fracture treatment. Reaming of the femoral canal might contribute to an enhanced "second hit" response after trauma. Consequently, the choice of fracture treatment might imply the clinical outcome of the critically injured patients and might be therefore crucial for their survival.

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Section: Discussionsupporting

confidence: 88%

Complement Activation and Organ Damage After Trauma—Differential Immune Response Based on Surgical Treatment Strategy

et al. 2020

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“…Thereby, the conductance of Cx43 may be reduced by phosphorylation by the Ca 2+ -dependent protein kinase C (PKC) [80]. Moreover, in the present study, Cx43 was translocated from intercalated discs into the cytosol of the CMs (data not shown), which is in accordance to earlier studies in different trauma models, as well as in septic rodents and humans [18][19][20][21][22]. The translocation of the Cx43 was also demonstrated previously in ischemic as well as in nonischemic cardiac injury [81][82][83].…”

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confidence: 92%

“…However, little is known about the effects of sepsis on the expression and distribution of other cardiac gap and tight junction proteins and cardiac structure. In previous experiments, our group showed that severe trauma affected cardiac structure and the localization of gap junction proteins [21,22]. Furthermore, we demonstrated that multiple trauma in pigs altered the expression of cardiac structure proteins, such as α-actinin and desmin.…”

Section: Introductionmentioning

confidence: 67%

“…This translocation has been shown to lead to a loss of mechanical and electrical coupling of the CMs, finally resulting in cardiac dysfunction [22]. Further, Cx43 translocation was also observed in rats after blunt chest trauma [21], again indicating disrupted cardiac electrical coupling, resulting in arrhythmias [21,23]. In this study we investigated the effects of septic conditions on cardiac structure, gap junction, and tight junction proteins.…”

Section: Introductionmentioning

confidence: 95%

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Toll-Like Receptor-Mediated Cardiac Injury during Experimental Sepsis

Lackner

Weber

Chakraborty

et al. 2020

Mediators of Inflammation

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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.

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“…Because of their cardio-depressive effects, pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs) such as the high-mobility group box 1 (HMGB-1) protein and extracellular histones have been linked to post-traumatic cardiac dysfunction [6,[14][15][16]. A trend towards higher systemic concentrations of IL-6, plasma elastase, CD11b expression and soluble intercellular adhesion molecule 1 (s-ICAM-1) was found after femoral reaming, compared to non-reamed fracture stabilization [17].…”

Section: Introductionmentioning

confidence: 99%

Structural alterations and inflammation in the heart after multiple trauma followed by reamed versus non-reamed femoral nailing

et al. 2020

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Background Approximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus nonreamed femoral nailing) on cardiac alterations was studied. Experimental approach 15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro. Results After multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1

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Experimental blunt chest trauma-induced myocardial inflammation and alteration of gap-junction protein connexin 43

Cited by 29 publications

References 48 publications

Complement Activation and Organ Damage After Trauma—Differential Immune Response Based on Surgical Treatment Strategy

Complement Activation and Organ Damage After Trauma—Differential Immune Response Based on Surgical Treatment Strategy

Toll-Like Receptor-Mediated Cardiac Injury during Experimental Sepsis

Structural alterations and inflammation in the heart after multiple trauma followed by reamed versus non-reamed femoral nailing

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