Blockade of Hepatocyte PCSK9 Ameliorates Hepatic Ischemia-Reperfusion Injury by Promoting Pink1-Parkin–Mediated Mitophagy

Zhang, Yu; Wang, Ziyi; Jia, Chenyang; Yu, Wenjie; Li, Xiangdong; Xia, Nan; Nie, Huiling; Wikana, Likalamu Pascalia; Chen, Minhao; Ni, Yong; Han, Sheng; Pu, Liyong

doi:10.1016/j.jcmgh.2023.09.004

Cited by 9 publications

(3 citation statements)

References 50 publications

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“…С другой стороны, нормотермическая перфузия имитирует нормальные физиологические условия путем перфузии крови, температура которой 37°С. При такой температуре оксигенация необходима для поддержания метаболических процессов: печень получает оксигенированную кровь, нормальный клеточный метаболизм [12].…”

Section: история сохранения органовunclassified

“…В настоящее время с целью уменьшения последствий ИРП, улучшения выживаемости трансплантата, а также снижения дозировок препаратов иммуносупрессивной терапии (ИТ) и расширения пула донорских органов используется таргетная терапия, направленная на хорошо изученные звенья патогенеза. Так, в ряде экспериментальных исследований были выполнены успешные попытки влияния на антиоксидантную систему путем введения препаратов, воздействующих на ее различные компоненты [12,13].…”

Section: история сохранения органовunclassified

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Understudied targets of the ischemia-reperfusion injury pathogenesis in liver transplantation

Svishcheva,

Kanibolotskiy,

Yaremin

et al. 2024

Transplantologiâ (Mosk.)

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Background. Liver transplantation is currently the most effective method to treat diseases with end-stage liver failure. Complications are most often associated with the initially severe patient condition, imperfect organ preservation methods, the surgical management per se, and immune system incompetence. The most common complications of transplantation include ischemic reperfusion injury, which occurs to some or another extent in each transplanted organ and worsens the course of the postoperative period. The process is based on complex pathophysiological mechanisms of cell damage due to ischemia and inflammation caused by reperfusion.Objective. To summarize current data on the mechanisms of the ischemic reperfusion injury development in liver transplantation and to find the ways to reduce adverse effects.Material and methods. The analysis of data from foreign and homeland experimental and clinical studies on the pathogenesis of ischemic reperfusion injury in liver transplantation has been performed. The search for literature data was carried out in international databases (PubMed/MedLine, ResearchGate, as well as in the scientific electronic library of Russia (eLibrary.RU) for the period from 2020-2024.Conclusion. The analyzed publications have provided various algorithms for the preservation of donor organs, including those using machine perfusion.

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Section: история сохранения органовunclassified

Understudied targets of the ischemia-reperfusion injury pathogenesis in liver transplantation

Svishcheva,

Kanibolotskiy,

Yaremin

et al. 2024

Transplantologiâ (Mosk.)

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“… 1 , 2 , 3 , 4 IR injury (IRI) in liver is an inevitable outcome of liver transplantation and resection surgery, so understanding the pathogenesis of liver IRI is important for optimizing surgery success. 5 , 6 During hepatic IR, sudden intense oxidative stress and an inflammatory response can directly lead to hepatocyte injury and necrosis. 7 , 8 , 9 , 10 , 11 Inflammatory cytokines and chemokines produced by damaged hepatocytes are involved in the recruitment of immune cells to the liver, causing immune activation together with activation of the complement cascade, culminating in hepatic IRI.…”

Section: Introductionmentioning

confidence: 99%

A single‐chain antibody construct with specificity of a natural IgM antibody reduces hepatic ischemia reperfusion injury in mice

Yang,

Li,

Wang

et al. 2024

J Cellular Molecular Medi

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Natural immunoglobulin M (IgM) antibodies have been shown to recognize post‐ischemic neoepitopes following reperfusion of tissues and to activate complement. Specifically, IgM antibodies and complement have been shown to drive hepatic ischemia reperfusion injury (IRI). Herein, we investigate the therapeutic effect of C2 scFv (single‐chain antibody construct with specificity of a natural IgM antibody) on hepatic IRI in C57BL/6 mice. Compared with PBS‐treated mice, C2 scFv‐treated mice displayed almost no necrotic areas, significant reduction in serum ALT, AST and LDH levels, and significantly reduced in the number of TUNEL positive cells. Moreover, C2 scFv‐treated mice exhibited a notable reduction in inflammatory cells after hepatic IRI than PBS‐treated mice. The serum IL‐6, IL‐1β, TNF‐α and MPC‐1 levels were also severely suppressed by C2 scFv. Interestingly, C2 scFv reconstituted hepatic inflammation and IRI in Rag1−/− mice. We found that C2 scFv promoted hepatic cell death and increased inflammatory cytokines and infiltration of inflammatory cells after hepatic IRI in Rag1−/− mice. In addition, IgM and complement 3d (C3d) were deposited in WT mice and in Rag1−/− mice reconstituted with C2 scFv, indicating that C2 scFv can affect IgM binding and complement activation and reconstitute hepatic IRI. C3d expression was significantly lower in C57BL/6 mice treated with C2 scFv compared to PBS, indicating that excessive exogenous C2 scFv inhibited complement activation. These data suggest that C2 scFv alleviates hepatic IRI by blocking complement activation, and treatment with C2 scFv may be a promising therapy for hepatic IRI.

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Curcumin's Protective Role in Heatstroke‐Induced Acute Liver Injury: Targeting Pyroptosis and Enhancing SIRT1 Expression

Wu,

Guo,

et al. 2024

Global Challenges

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Heatstroke (HS) is a severe systemic condition that significantly impacts organ function, with the liver being particularly vulnerable. Sirtuin 1 (SIRT1), a crucial deacetylase, is implicated in various diseases' pathophysiology. Curcumin, a natural polyphenol, has been shown to modulate SIRT1 activity, offering therapeutic benefits. This study explores the impact of HS on hepatic SIRT1 expression and the protective mechanisms of curcumin against HS‐induced hepatic injury. Male C57BL/6 mice are divided into control and curcumin pretreatment groups, subjected to HS induction, and assessed for liver injury biomarkers, oxidative stress, and inflammatory cytokines. Results indicate that HS downregulates SIRT1, leading to liver damage and systemic inflammation. Curcumin pretreatment dose‐responsively attenuates these effects, with the highest dose providing optimal protection, potentially through SIRT1 restoration. The findings suggest that curcumin's hepatoprotective role in HS may be mediated by upregulating SIRT1, highlighting its therapeutic potential in heatstroke‐related liver damage.

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Blockade of Hepatocyte PCSK9 Ameliorates Hepatic Ischemia-Reperfusion Injury by Promoting Pink1-Parkin–Mediated Mitophagy

Cited by 9 publications

References 50 publications

Understudied targets of the ischemia-reperfusion injury pathogenesis in liver transplantation

Understudied targets of the ischemia-reperfusion injury pathogenesis in liver transplantation

A single‐chain antibody construct with specificity of a natural IgM antibody reduces hepatic ischemia reperfusion injury in mice

Curcumin's Protective Role in Heatstroke‐Induced Acute Liver Injury: Targeting Pyroptosis and Enhancing SIRT1 Expression

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