Abstract
AbstractStress cardiomyopathy is a major clinical complication after severe burn. Multiple upstream initiators have been identified; however, the downstream targets are not fully understood. This study assessed the role of the plasma membrane in this process and its relationship with the protease μ-calpain and tumor necrosis factor-alpha (TNF-α). Here, third-degree burn injury of approximately 40% of the total body surface area was established in rats. Plasma levels of LDH and cTnI and cardiac cell apoptosis increased at 0.5 h post burn, reached a peak at 6 h, and gradually declined at 24 h. This effect correlated well with not only the disruption of cytoskeletal proteins, including dystrophin and ankyrin-B, but also with the activation of μ-calpain, as indicated by the cleaved fragments of α-spectrin and membrane recruitment of the catalytic subunit CAPN1. More importantly, these alterations were diminished by blocking calpain activity with MDL28170. Burn injury markedly increased the cellular uptake of Evans blue, indicating membrane integrity disruption, and this effect was also reversed by MDL28170. Compared with those in the control group, cardiac cells in the burn plasma-treated group were more prone to damage, as indicated by a marked decrease in cell viability and increases in LDH release and apoptosis. Of note, these alterations were mitigated by CAPN1 siRNA. Moreover, after neutralizing TNF-α with rhTNFR:Fc, calpain activity was blocked, and heart function was improved. In conclusion, we identified μ-calpain as a trigger for severe burn-induced membrane disruption in the heart and provided evidence for the application of rhTNFR:Fc to inhibit calpain for cardioprotection.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Reference44 articles.
1. Gawande NB, Tumram NK, Dongre AP. Cardiac changes in hospitalized patients of trauma. Shock. 2014;42:211–7.
2. Rehou S, Shahrokhi S, Thai J, Stanojcic M, Jeschke MG. Acute phase response in critically ill elderly burn patients. Crit Care Med. 2019;47:201–9.
3. Guillory AN, Clayton RP, Herndon DN, Finnerty CC. Cardiovascular dysfunction following burn injury: What we have learned from rat and mouse models. Int J Mol Sci. 2016;17:53.
4. Xiao R, Lei ZY, Dang YM, Huang YS. Prompt myocardial damage contributes to hepatic, renal, and intestinal injuries soon after a severe burn in rats. Trauma. 2011;71:663–71.
5. Lin CY, Wu CK, Yeong EK, Lin HH, Huang YT, Lee JK, et al. Prognostic significance of left ventricular diastolic function in burn patients. Shock. 2012;37:457–62.
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献