Necrostatin‐1 alleviates reperfusion injury following acute myocardial infarction in pigs

Koudstaal, Stefan; Oerlemans, M. I. F. J.; Spoel, Tycho I.G. van der; Janssen, Aafke W. F.; Hoefer, Imo E.; Doevendans, Pieter A.; Sluijter, Joost P.G.; Chamuleau, Steven A.J.

doi:10.1111/eci.12391

Cited by 72 publications

(50 citation statements)

References 27 publications

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“…Accordingly, both Camk2g −/− and Ppif −/− mice are remarkably protected from cardiac I/R and/or cardiotoxic chemotherapy (113, 114, 140). Nec-1 also mediates cardioprotective activity in mouse and pig models of cardiac I/R (113, 141, 142), but it remains unclear whether such an effect truly stems from the inhibition of Ripk3-dependent necroptosis (113). Ripk3 −/− and Ripk3 + / − mice are more resistant to elastase-induced abdominal aortic aneurysm than are their WT littermates, a protective effect that can also be observed upon transplantation of Ripk3 + / − aortae into WT recipients and that involves a reduced loss of smooth muscle cells as well as a limited expression of proinflammatory genes (143).…”

Section: Pathophysiological Relevance Of Necroptosismentioning

confidence: 99%

Necroptosis: Mechanisms and Relevance to Disease

Galluzzi

Kepp

Chan

2017

Annu. Rev. Pathol. Mech. Dis.

538

398

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Necroptosis is a form of regulated cell death that critically depends on receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) and generally manifests with morphological features of necrosis. The molecular mechanisms that underlie distinct instances of necroptosis have just begun to emerge. Nonetheless, it has already been shown that necroptosis contributes to cellular demise in various pathophysiological conditions, including viral infection, acute kidney injury, and cardiac ischemia/reperfusion. Moreover, human tumors appear to obtain an advantage from the downregulation of key components of the molecular machinery for necroptosis. Although such an advantage may stem from an increased resistance to adverse microenvironmental conditions, accumulating evidence indicates that necroptosis-deficient cancer cells are poorly immunogenic and hence escape natural and therapy-elicited immunosurveillance. Here, we discuss the molecular mechanisms and relevance to disease of necroptosis.

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Section: Pathophysiological Relevance Of Necroptosismentioning

confidence: 99%

Necroptosis: Mechanisms and Relevance to Disease

Galluzzi

Kepp

Chan

2017

Annu. Rev. Pathol. Mech. Dis.

538

398

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“…Several studies showed strong protection from heart IRI injury by Nec-1 in different animal models [92-94]. Multiple reports also demonstrated strong amelioration of the injury in Ripk3 -/- mice [83, 95, 96].…”

Section: Disease Pathologymentioning

confidence: 99%

Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis

Wegner

Saleh

Degterev

2017

Trends in Pharmacological Sciences

144

132

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A process of regulated necrosis, termed necroptosis, has been recognized as a major contributor to cell death and inflammation occurring under a wide range of pathologic settings. The core event in necroptosis is the formation of the detergent-insoluble “necrosome” complex of homologous Ser/Thr kinases Receptor Interacting Kinase 1 (RIPK1) and Receptor Interacting Kinase 3 (RIPK3), which promotes phosphorylation of a key pro-death effector Mixed Lineage Kinase Domain-like (MLKL) by RIPK3. Core necroptosis mediators are under multiple controls, which have been a subject of intense investigation. Additional, non-necroptotic functions of these factors, primarily in controlling apoptosis and inflammatory responses, have also begun to emerge. This review will provide an overview of the current understanding of the human disease relevance of this pathway, and potential therapeutic strategies, targeting necroptosis mediators in various pathologies.

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“…This protein complex evolves to the necroptosome after disassociation from the death receptor, and association of proteins, including, RIP1 and RIP3 [52, 53, 56, 57]. Necrostatin, a RIP1 inhibitor, has been shown to protect against myocardial ischemia-reperfusion injury [58, 59]. The downstream signaling pathways of RIP1/RIP3 complex are less understood, but are increasingly studied.…”

Section: Introductionmentioning

confidence: 99%

CaMKII is a nodal signal for multiple programmed cell death pathways in heart

Feng

Anderson

2017

Journal of Molecular and Cellular Cardiology

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Sustained Ca2+/calmodulin dependent kinase II (CaMKII) activation plays a central role in the pathogenesis of a variety of cardiac diseases. Emerging evidence suggests CaMKII evoked programmed cell death, including apoptosis and necroptosis, is one of the key underlying mechanisms for the detrimental effect of sustained CaMKII activation. CaMKII integrates β-adrenergic, Gq coupled receptor, reactive oxygen species (ROS), hyperglycemia, and pro-death cytokine signaling to elicit myocardial apoptosis by intrinsic and extrinsic pathways. New evidence demonstrates CaMKII is also a key mediator of receptor interacting serine/threonine kinase 3 (RIP3) induced myocardial necroptosis. The role of CaMKII in cell death is dependent upon subcellular localization and varies across isoforms and splice variants. While CaMKII is now an extensively validated nodal signal for promoting cardiac myocyte death, the upstream and downstream pathways and targets remain incompletely understood, demanding further investigation.

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Necrostatin‐1 alleviates reperfusion injury following acute myocardial infarction in pigs

Cited by 72 publications

References 27 publications

Necroptosis: Mechanisms and Relevance to Disease

Necroptosis: Mechanisms and Relevance to Disease

Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis

CaMKII is a nodal signal for multiple programmed cell death pathways in heart

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