MCP-1 mediates ischemia-reperfusion-induced cardiomyocyte apoptosis via MCPIP1 and CaSR

Zhang, Wei; Zhu, Tongyu; Chen, Lulu; Luo, Wei; Chao, Jie

doi:10.1152/ajpheart.00308.2019

Cited by 32 publications

(16 citation statements)

References 48 publications

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“…It has also been suggested that CCL2 may exert direct actions on cardiomyocytes, increasing injury-associated death and promoting dysfunction. Some studies have suggested that CCL2 may promote cardiomyocyte apoptosis through induction of the ribonuclease monocyte chemoattractant protein-1-induced protein (MCPIP, originally proposed to function as a transcription factor), also known as regnase-1 [ 145 , 146 ]. However, regnase-1/MCPIP can be induced by a wide range of inflammatory mediators, and is known to restrain inflammation by degrading cytokine RNAs in immune and non-immune cells [ 147 ].…”

Section: Ccl2 and The Chemokinesmentioning

confidence: 99%

Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Hanna

Frangogiannis

2020

Cardiovasc Drugs Ther

249

170

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Heart failure exhibits remarkable pathophysiologic heterogeneity. A large body of evidence suggests that regardless of the underlying etiology, heart failure is associated with induction of cytokines and chemokines that may contribute to the pathogenesis of adverse remodeling, and systolic and diastolic dysfunction. The pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 have been extensively implicated in the pathogenesis of heart failure. Inflammatory cytokines modulate phenotype and function of all myocardial cells, suppressing contractile function in cardiomyocytes, inducing inflammatory activation in macrophages, stimulating microvascular inflammation and dysfunction, and promoting a matrixdegrading phenotype in fibroblasts. Moreover, cytokine-induced growth factor synthesis may exert chronic fibrogenic actions contributing to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In addition to their role in adverse cardiac remodeling, some inflammatory cytokines may also exert protective actions on cardiomyocytes under conditions of stress. Chemokines, such as CCL2, are also upregulated in failing hearts and may stimulate recruitment of pro-inflammatory leukocytes, promoting myocardial injury, fibrotic remodeling, and dysfunction. Although experimental evidence suggests that cytokine and chemokine targeting may hold therapeutic promise in heart failure, clinical translation remains challenging. This review manuscript summarizes our knowledge on the role of TNF-α, IL-1, IL-6, and CCL2 in the pathogenesis of heart failure, and discusses the promises and challenges of targeted anti-cytokine therapy. Dissection of protective and maladaptive cellular actions of cytokines in the failing heart, and identification of patient subsets with overactive or dysregulated myocardial inflammatory responses are required for design of successful therapeutic approaches.

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Section: Ccl2 and The Chemokinesmentioning

confidence: 99%

Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Hanna

Frangogiannis

2020

Cardiovasc Drugs Ther

249

170

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“…Indeed, recent studies reported the expression and release of Ccl2 from cardiomyocytes in response to I/R by inflammatory mediators. 36,37…”

Section: Resultsmentioning

confidence: 99%

“…We identified the monocyte-attracting chemokine Ccl2 as a target regulated by the mTORC1-4EBP1-eIF4F pathway that was expressed by a subset of cardiomyocytes exclusively in response to reperfusion, as has been recently described for isolated cardiomyocytes. 36,37 Inhibition of the CCR2-CCL2 axis was previously shown to exhibit beneficial effects in murine models of myocardial infarction. 48 In addition, mTORC1 was previously described to regulate (which was not certified by peer review) is the author/funder.…”

Section: Translational Regulation Of Myocardial Inflammation In Respo...mentioning

confidence: 99%

“…Indeed, recent studies reported the expression and release of Ccl2 from cardiomyocytes in response to I/R by inflammatory mediators. 36,37 To further investigate the expression of Ccl2 in cardiac cells in response to I/R in vivo, we analyzed an I/R time course of single-cell transcriptomics in mice recently published by Molenaar et al 38 (Online Figure 10). We have made our analysis publicly available using the shinycell 39 interactive web application accessible at https://shiny.jakobilab.org/Hofmann_et_al_2022/.…”

Section: Elevatedmentioning

confidence: 99%

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Transient inhibition of translation improves long-term cardiac function after ischemia/reperfusion by attenuating the inflammatory response

Hofmann

Serafin

Schwerdt

et al. 2022

Preprint

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Rationale: Rapid reperfusion is the most effective treatment for attenuating cardiac injury caused by myocardial ischemia. Yet, reperfusion itself elicits damage to the myocardium through incompletely understood mechanisms, known as ischemia/reperfusion (I/R) injury. The myocardium adapts to I/R by changes in gene expression, which determines the cellular response to reperfusion. Protein translation is a key component of gene expression. However, it is unknown how regulation of translation contributes to cardiac gene expression in response to reperfusion and whether it can be targeted to mitigate I/R injury. Methods: To examine translation and its impact on gene expression in response to I/R we assessed protein synthesis at different timepoints after ischemia and reperfusion in vitro and in vivo. Pharmacological inhibitors were used to dissect the underlying molecular mechanisms of translational control. Transient inhibition of protein synthesis was undertaken to decipher the effects of the translational response to reperfusion on cardiac function and inflammation. Cell-type-specific ribosome profiling was performed in mice subjected to I/R to determine the impact of translation on the regulation of gene expression in cardiomyocytes. Results: Reperfusion increased translation rates from a previously suppressed state during ischemia in cardiomyocytes, which was associated with the induction of cell death. In vivo, I/R resulted in strong activation of translation in the myocardial border zone. Detailed analysis revealed that the upregulation of translation is mediated by eIF4F complex formation, which was specifically mediated by the mTORC1-4EBP1-eIF4F axis. Short-term pharmacological inhibition of eIF4F complex formation by 4EGI-1 or rapamycin, respectively, attenuated translation, reduced infarct size and improved long-term cardiac function after myocardial infarction. Cardiomyocyte-specific ribosome profiling identified that reperfusion damage increased translation of mRNA networks in cardiomyocytes associated with cardiac inflammation and cell infiltration. Transient inhibition of the mTORC1-4EBP1-eIF4F axis decreased the expression of proinflammatory transcripts such as Ccl2, thereby reducing Ly6Chi monocyte infiltration and myocardial inflammation. Conclusions: Myocardial reperfusion induces protein synthesis in the border zone which contributes to I/R injury by rapidly translating a specific maladaptive mRNA network that mediates immune cell infiltration and inflammation. Transient inhibition of the mTORC1-4EBP1-eIF4F signaling axis during reperfusion attenuates this proinflammatory translational response, protects against I/R injury and improves long-term cardiac function after myocardial infarction.

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“…Although the migration pathway of chemotactic PMN to the site of myocardial injury cannot be fully described, the role of PMN activation in the pathogenesis of cardiovascular disease is clear. PMN was recruited to the infarct area very early, they play a role by adhering to vascular endothelial cells through molecules of selectins, integrins and immunoglobulin superfamily [39]. Once adhered to the infarct area, PMN will release ROS, cytokines and proteolytic enzymes, resulting in the increase of MDA level and the decrease of SOD level [40].…”

Section: Discussionmentioning

confidence: 99%

Over-expression of SDF-1α on BMSCs Reduce the Injury Caused by PMN in Myocardial Ischemia/reperfusion

Wang¹,

Wen²,

Rong³

et al. 2021

Preprint

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Background: To study the protective effect of BMSC overexpressing SDF-1α on myocardial ischemia/reperfusion (I/R), to improve the limitation that only part of BMSC is recruited to the site of myocardial injury in the treatment of ischemic heart disease. It provides a new scheme for stem cell therapy for clinical treatment of reperfusion injury.Methods: Collect blood samples from PCI patients and healthy individuals to detect PMN and SDF-1α expression; Construction of BMSC overexpressing SDF-1α (oe-SDF-1α); In the case of no intervention or intervention by BMSC respectively, cell level: the migration ability of PMN to hypoxia/reoxygenation (H/R) cardiomyocytes and the expression of SDF-1α, CXCR4, apoptosis, oxidative stress and other indicators of cardiomyocytes were detected; In vivo level: PMN, SDF-1α, CXCR4, oxidative stress and inflammatory factor levels were detected in I/R mice. And carry out statistical analysis.Results: ① In the clinic, compared with the control group, the expression levels of SDF-1α and PMN in the blood of PCI patients increased. ② Under H/R conditions, cardiomyocytes express and secrete SDF-1α, activate PMN migration and infiltration mediated by SDF-1/CXCR4 signal pathway, promote cardiomyocyte apoptosis and increase the level of oxidative stress; oe-SDF-1α has a stronger ability to migrate to H/R cardiomyocytes and has more repair ability than BMSC.It is more suitable as a tool cell for stem cell therapy. ③ The expression levels of SDF-1α and PMN are increased in I/R mice. oe-SDF-1α can reduce the ability of PMN to reside to the damaged part of myocardial tissue significantly, thereby reducing myocardial tissue damage, oxidative stress, inflammatory factor levels in I/R mice. Conclusions: The SDF-1/CXCR4 biological axis not only plays an important role in BMSC migration, but also helps to enhance the therapeutic effect of BMSC-based therapy. Oe-SDF-1α has a more repairing effect on reducing cell damage caused by PMN, and can be used as a new type of cell for the treatment of IRI.

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MCP-1 mediates ischemia-reperfusion-induced cardiomyocyte apoptosis via MCPIP1 and CaSR

Cited by 32 publications

References 48 publications

Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Transient inhibition of translation improves long-term cardiac function after ischemia/reperfusion by attenuating the inflammatory response

Over-expression of SDF-1α on BMSCs Reduce the Injury Caused by PMN in Myocardial Ischemia/reperfusion

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