Role of necroptosis in the pathogenesis of solid organ injury

Zhao, Hailin; Jaffer, Tanweer; Eguchi, Shiori; Wang, Z; Linkermann, Andreas; Ma, Daqing

doi:10.1038/cddis.2015.316

Cited by 121 publications

(92 citation statements)

References 110 publications

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“…However, the inflammatory and cell death responses triggered by RIPK3 represent a double-edged sword, and their aberrant activation may contribute to tissue pathology. Consistent with this idea, there is accumulating evidence that acute or chronic organ injury can lead to RIPK3-dependent contributions to the pathophysiology of a variety of diseases (reviewed in 75 ). Interestingly, evidence from knockout mice has highlighted the differing contributions of MLKL and RIPK3 to these pathologies, supporting the idea that non-necroptotic functions of RIPK3 may underlie some of the observed effects.…”

Section: Contributions Of Ripk3 To Tissue Damagementioning

confidence: 87%

RIPK3 in cell death and inflammation: the good, the bad, and the ugly

Orozco

Oberst

2017

Immunological Reviews

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Summary Necroptosis is a form of cell death that can be observed downstream of death receptor or pattern recognition receptor signaling under certain cellular contexts, or in response to some viral and bacterial infections. The receptor interacting protein kinases-1 (RIPK1) and RIPK3 are at the core of necroptotic signaling, among other proteins. Because this pathway is normally halted by the pro-apoptotic protease caspase-8 and the IAP ubiquitin ligases, how and when necroptosis is triggered in physiological settings are ongoing questions. Interestingly, accumulating evidence suggests that RIPK3 has functions beyond the induction of necroptotic cell death, especially in the areas of tissue injury and sterile inflammation. Here, we will discuss the role of RIPK3 in a variety of physiological conditions, including necroptotic and non-necroptotic cell death, in the context of viral and bacterial infections, tissue damage, and inflammation.

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Section: Contributions Of Ripk3 To Tissue Damagementioning

confidence: 87%

RIPK3 in cell death and inflammation: the good, the bad, and the ugly

Orozco

Oberst

2017

Immunological Reviews

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“…These morphological observations are partially inconsistent with experimental data in healthy elderly persons showing that ageing is related to an increased proinflammatory status . A primary feature of the ageing process, as discussed above, is a chronic progressive increase in the proinflammatory status, which was originally termed ‘inflamm‐ageing’ .The cause of the increased proinflammatory status is related to elevated circulating levels of proinflammatory cytokines including IL‐1, IL‐6, TNF‐α and PGE2, which have a major role in pathology . The increased plaque vulnerability in elderly patients is probably correlated with several mechanisms (some of which are linked to the release of inflammatory cytokines), such as endothelial adhesion of inflammatory cells, increased absorption of atherogenic lipoprotein, increase in the necrotic lipid core and calcification of plaque.…”

Section: Plaque Morphology and Ageingmentioning

confidence: 94%

Arterial ageing: from endothelial dysfunction to vascular calcification

et al. 2017

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Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to ‘synthetic’ determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low‐level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well‐established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing‐related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed.

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“…A large number of studies have shown that cell death is an important component in the pathogenesis of various cardiovascular diseases (Tavernarakis, ; Dorn, ; Karch and Molkentin, ; Zhao et al ., ). This discussion now mainly focuses on cardiac myocytes, although a variety of other cell types are also involved.…”

Section: Programmed Cardiomyocyte Necrosis In Cardiovascular Diseasesmentioning

confidence: 97%

Programmed necrosis in cardiomyocytes: mitochondria, death receptors and beyond

Zhang

Liu

Zhang

et al. 2018

British J Pharmacology

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Excessive death of cardiac myocytes leads to many cardiac diseases, including myocardial infarction, arrhythmia, heart failure and sudden cardiac death. For the last several decades, most work on cell death has focused on apoptosis, which is generally considered as the only form of regulated cell death, whereas necrosis has been regarded to be an unregulated process. Recent findings reveal that necrosis also occurs in a regulated manner and that it is closely related to the physiology and pathophysiology of many organs, including the heart. The recognition of necrosis as a regulated process mandates a re‐examination of cell death in the heart together with the mechanisms and therapy of cardiac diseases. In this study, we summarize the regulatory mechanisms of the programmed necrosis of cardiomyocytes, that is, the intrinsic (mitochondrial) and extrinsic (death receptor) pathways. Furthermore, the role of this programmed necrosis in various heart diseases is also delineated. Finally, we describe the currently known pharmacological inhibitors of several of the key regulatory molecules of regulated cell necrosis and the opportunities for their therapeutic use in cardiac disease. We intend to systemically summarize the recent progresses in the regulation and pathological significance of programmed cardiomyocyte necrosis along with its potential therapeutic applications to cardiac diseases. Linked Articles This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc

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Role of necroptosis in the pathogenesis of solid organ injury

Cited by 121 publications

References 110 publications

RIPK3 in cell death and inflammation: the good, the bad, and the ugly

RIPK3 in cell death and inflammation: the good, the bad, and the ugly

Arterial ageing: from endothelial dysfunction to vascular calcification

Programmed necrosis in cardiomyocytes: mitochondria, death receptors and beyond

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