Membrane Attack Complex in Myocardial Ischemia/Reperfusion Injury: A Systematic Review for Post Mortem Applications

Mondello, Cristina; Spagnolo, Elvira Ventura; Cardia, Luigi; Sapienza, Daniela; Scurria, Serena; Gualniera, Patrizia; Asmundo, Alessio

doi:10.3390/diagnostics10110898

Cited by 10 publications

(6 citation statements)

References 63 publications

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“…Moreover, this would be supported by C5b-9 involvement in pathologies as antiphospholipid antibody syndrome and purpura fulminans ( Perera and Murphy-Lavoie, 2020 ; Ruffatti et al, 2020 ). MAC contributes to endothelial activation, resulting in cell adhesion molecules and releasing chemotactic and activating factors related to migration and activation of white cells ( Kilgore et al, 1995 ; Mondello et al, 2017 ; Mondello et al, 2018 ; Mondello et al, 2020 ). The role of the complement system in lung injuries due to SARS-CoV-2 was also supported by the immunohistochemical detection of MASP-2 (mannan-binding lectin-associated serine protease-2) ( Magro et al, 2020 ), an effector enzyme of the lectin pathways capable of binding the SARS-CoV-2 nucleocapsid protein, resulting in complement activation and endothelial/tissue injury ( Rambaldi et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review

et al. 2021

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Introduction: The World Health Organization declared the COVID-19 pandemic in March 2020. COVID-19 still represents a worldwide health emergency, which causesa severe disease that has led to the death of many patients. The pathophysiological mechanism of SARS-CoV-2 determining the tissue damage is not clear and autopsycan be auseful tool to improve the knowledge of this infection and, thus, it can help achieve a timely diagnosis and develop an appropriate therapy. This is an overview of the main post-mortem findings reporting data on the infection effects on several organs.Methods: A systematic literature search was conducted in the PubMed database searching for articles from 1 January to August 31, 2020. Thearticles were selected identifying words/concepts in the titles and/or abstracts that indicated the analysis of the morphological/pathological tissue injuries related to SARS-CoV-2 disease by several investigations.Results: A total of 63 articles were selected. The main investigated tissue was the lung showing a diffuse alveolar damage (DAD) frequently associated with pulmonary thrombotic microangiopathy. Inflammatory findings and vascular damage were observed in other organs such as heart, liver, kidney, brain, spleen, skin and adrenal gland. The immunohistochemical analysis showed tissue inflammatory cells infiltrates. The virus presence was detected by several investigations such as RT-PCR, immunohistochemistry and electron microscope, showing the effect ofSARS-CoV-2not exclusively in the lung.Discussion: The evidence emerging from this review highlighted the importance of autopsy to provide a fundamental base in the process of understanding the consequences ofSARS-CoV-2 infection. COVID-19 is strictly related to a hyper inflammatory state that seems to start with DAD and immuno-thrombotic microangiopathy. Massive activation of the immune system and microvascular damage might also be responsible for indirect damage to other organs, even if the direct effect of the virus on these tissues cannot be excluded.

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Section: Discussionmentioning

confidence: 99%

Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review

et al. 2021

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“…The contribution of the activation of the complement system to cardiomyocyte damage has been investigated in many studies [ 15 ]. Studies have shown that with complement-mediated damage and ischemic injury, CD59 loss in the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

The Role of Immunohistochemical Markers in the Diagnosis of Early Myocardial Infarction

Buğra¹,

Daş²

2022

Cureus

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Introduction: Pathological diagnosis of acute myocardial infarction can be difficult if death from ischemic injury has occurred within a short period of time. In this study, we aimed to determine the role of immunohistochemical markers in the diagnosis of early myocardial infarction.Methods: The myocardium samples of 20 cases whose autopsies were performed at the Morgue Department of the Council of Forensic Medicine were evaluated. Hematoxylin and Eosin (H&E) stained slides and fibronectin, CD59, myoglobulin, troponin T, desmin, cathepsin S stained slides of 20 cases diagnosed with early myocardial infarction were retrospectively re-examined. The diagnosis of myocardial infarction was analyzed in two groups: Group 1: first eight hours, Group 2: 8-24 hours. The immunohistochemical staining patterns in these two groups were compared.Results: Of the cases, 55% (n=11) had myocardial infarction consistent with the first eight hours, 45% (n=9) 8-24 hours with light microscopic examination. With fibronectin, 50% (n=10) of the cases showed Grade 1 staining, 5% (n=1) Grade 2, 15% (n=6) Grade 3 staining. The slides of three cases could not be reached. With CD59, 10% (n=2) of the cases showed Grade 1, 10% (n=2) Grade 2, 80% (n=16) Grade 3 staining. With troponin T, 50% (n=10) of the cases showed Grade 1, 45% (n=9) Grade 2, 5% (n=1) Grade 3 depletion. With cathepsin S, 10% (n=2) of the cases showed Grade 1 and 80% (n=16) Grade 3 depletion. The slides of two cases could not be reached. With desmin, 75% (n=15) had Grade 1 and 25% (n=5) Grade 2 depletion. Grade 3 depletion with myoglobulin was observed in all cases. Conclusion:The diagnosis of early myocardial infarction, which may pose a problem for the forensic pathologist, may become easier with immunohistochemical methods. In cases where morphological findings are insufficient, it is more useful for diagnosis to be applied as a panel.

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“…Increasing evidence shows that complement activation plays an important role in myocardial I/R injury [ 32 ]. After activation, the terminal complement components C5a and C5b-9 are deposited in the ischemic area and induce myocardial necrosis [ 33 ]. Furthermore, C5a also promotes immune responses by accumulating inflammatory cells and releasing pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, thereby causing indirect myocardial damage [ 15 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB

Wang

Zhong

et al. 2021

Open Medicine

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Background Activation of the complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling is an important feature of myocardial ischemia/reperfusion (I/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-κB in MP-induced cardioprotection. Methods Male Sprague Dawley rats (n = 160) were randomized into eight groups (n = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150 min), and the other seven groups were subjected to 30 min of anterior descending coronary artery occlusion followed by 2 h of reperfusion and the following treatments: I/R (30 min of ischemia and followed by 2 h of reperfusion); ischemic postconditioning (IPostC, 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h); MP (0.3 mg/kg morphine administration 10 min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1 mg/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20 mg/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1 mg/kg/day, administration via drinking water for 28 days) and MP combined with the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion. Results MP significantly reduced the I/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1β, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-κB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection. Conclusion HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.

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Membrane Attack Complex in Myocardial Ischemia/Reperfusion Injury: A Systematic Review for Post Mortem Applications

Cited by 10 publications

References 63 publications

Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review

Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review

The Role of Immunohistochemical Markers in the Diagnosis of Early Myocardial Infarction

New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB

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