The impact of hyperglycaemia on PKM2-mediated NLRP3 inflammasome/stress granule signalling in macrophages and its correlation with plaque vulnerability: an in vivo and in vitro study

Li, Qinxue; Leng, Kunkun; Liu, Yayun; Sun, Haiyan; Gao, Jinhuan; Ren, Quanxin; Zhou, Tian; Dong, Jing; Xia, Jinggang

doi:10.1016/j.metabol.2020.154231

Cited by 31 publications

(30 citation statements)

References 24 publications

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“…In recent years, increased attention has been given to the role of aerobic glycolysis in atherosclerosis, especially the promotion of atherosclerosis occurrence and development by diabetes 15,16 . Our team's recent human clinical, animal, and cell studies showed that aerobic glycolysis‐related metabolic inflammation plays an important role in diabetes‐induced atherosclerosis 2,17 . However, the regulatory mechanism of glycolysis is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 Our team's recent human clinical, animal, and cell studies showed that aerobic glycolysis-related metabolic inflammation plays an important role in diabetes-induced atherosclerosis. 2,17 However, the regulatory mechanism of glycolysis is not clear. Our study further confirmed the role of Warburg effect-related inflammation on the complexity of coronary atherosclerosis.…”

Section: Oct and Histological Analysismentioning

confidence: 99%

“…The Warburg effect, 1 that is, aerobic glycolysis, is involved in the mechanism of atherosclerosis and has attracted attention. Recent research by our team 2 revealed that hyperglycemia might increase plaque vulnerability and lead to a worse prognosis via activation of pyruvate kinase M2 (PKM2)‐mediated inflammation, which is Warburg effect‐regulated inflammation. However, the mechanism by which hyperglycemia activates the metabolic inflammatory response has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Activation of macrophage TBK1‐HIF‐1α‐mediated IL‐17/IL‐10 signaling by hyperglycemia aggravates the complexity of coronary atherosclerosis: An in vivo and in vitro study

Liu

Xia

et al. 2021

FASEB j.

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Our purpose was to study the effect of hyperglycemia on macrophage TBK1-HIF-1αmediated IL-17/IL-10 signaling and its correlation with coronary atherosclerosis. A total of 135 patients with coronary heart disease (CHD) were divided into a stable CHD (SCHD) group (n = 30) and an acute myocardial infarction (AMI) group (n = 105) [nondiabetes mellitus (non-DM)-AMI, n = 60; DM-AMI, n = 45] from January to September 2020. The SYNTAX score and metabolic and inflammatory markers were quantified and compared. THP-1 cell studies and an animal study of coronary intimal hyperplasia were also carried out. We found that the DM-AMI group showed a higher SYNTAX score than the non-DM-AMI group (P < .05). The DM-AMI group showed the highest expression levels of TANK-binding kinase 1 (TBK1), hypoxia-inducible factor 1α (HIF-1α), and interleukin (IL)-17 and the lowest expression level of IL-10, followed by the non-DM-AMI group and the SCHD group (P < .05). THP-1 cell studies showed that BAY87-2243 (a HIF-1α inhibitor) reversed the increase in IL-17 and decrease in IL-10 expression induced by hyperglycemia. Amlexanox (a TBK1 inhibitor) reversed the increase in HIF-1α expression induced by hyperglycemia. Amlexanox treatment resulted in lower coronary artery intimal hyperplasia and a larger lumen area in a diabetic swine model. We conclude that hyperglycemia might aggravate the complexity of coronary atherosclerosis through activation of TBK1-HIF-1α-mediated IL-17/IL-10 signaling.Thus, TBK1 may be a novel drug therapy target for CHD complicated with DM.

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Section: Discussionmentioning

confidence: 99%

Section: Oct and Histological Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activation of macrophage TBK1‐HIF‐1α‐mediated IL‐17/IL‐10 signaling by hyperglycemia aggravates the complexity of coronary atherosclerosis: An in vivo and in vitro study

Liu

Xia

et al. 2021

FASEB j.

Self Cite

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“…Therefore, activating stress granules through the PKM2 axis to prevent inflammatory cell death is a potential therapy for inflammatory diseases. Studies have shown that hyperglycaemia increases the activation of PKM2-mediated NLRP3 inflammasomes and stress granule signalling, thus increasing plaque vulnerability and is associated with poor prognosis ( 149 ).…”

Section: Pkm2: a Potential Promotor Of Proinflammatory Non-apoptotic-regulated Cell Deathmentioning

confidence: 99%

Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm

Liu

Chen

et al. 2021

Front. Immunol.

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The cytokine storm is a marker of severity of various diseases and increased mortality. The altered metabolic profile and energy generation of immune cells affects their activation, exacerbating the cytokine storm. Currently, the emerging field of immunometabolism has highlighted the importance of specific metabolic pathways in immune regulation. The glycolytic enzyme pyruvate kinase M2 (PKM2) is a key regulator of immunometabolism and bridges metabolic and inflammatory dysfunction. This enzyme changes its conformation thus walks in different fields including metabolism and inflammation and associates with various transcription factors. This review summarizes the vital role of PKM2 in mediating immunometabolic reprogramming and its role in inducing cytokine storm, with a focus on providing references for further understanding of its pathological functions and for proposing new targets for the treatment of related diseases.

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“…Also, IS-induced mitochondrial dysfunction in cardiomyocytes causes the loss of mitochondrial membrane potential and release of mitochondrial DNA into the cytosol, which further activates NLRP3 inflammasome (54). Furthermore, hyperglycemia can also activate NLRP3 inflammasome in the myocardium (108). Overall, the cardiac NLRP3 inflammasome may be more sensitive to be activated in diabetic CCS.…”

Section: Nlrp3 Inflammasome Activation Induced Cardiac Damage In Diabetic Cerebral-cardiac Syndromementioning

confidence: 99%

Cerebral-Cardiac Syndrome and Diabetes: Cardiac Damage After Ischemic Stroke in Diabetic State

Lin

Zhang

et al. 2021

Front. Immunol.

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Cerebral-cardiac syndrome (CCS) refers to cardiac dysfunction following varying brain injuries. Ischemic stroke is strongly evidenced to induce CCS characterizing as arrhythmia, myocardial damage, and heart failure. CCS is attributed to be the second leading cause of death in the post-stroke stage; however, the responsible mechanisms are obscure. Studies indicated the possible mechanisms including insular cortex injury, autonomic imbalance, catecholamine surge, immune response, and systemic inflammation. Of note, the characteristics of the stroke population reveal a common comorbidity with diabetes. The close and causative correlation of diabetes and stroke directs the involvement of diabetes in CCS. Nevertheless, the role of diabetes and its corresponding molecular mechanisms in CCS have not been clarified. Here we conclude the features of CCS and the potential role of diabetes in CCS. Diabetes drives establish a “primed” inflammatory microenvironment and further induces severe systemic inflammation after stroke. The boosted inflammation is suspected to provoke cardiac pathological changes and hence exacerbate CCS. Importantly, as the key element of inflammation, NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is indicated to play an important role in diabetes, stroke, and the sequential CCS. Overall, we characterize the corresponding role of diabetes in CCS and speculate a link of NLRP3 inflammasome between them.

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The impact of hyperglycaemia on PKM2-mediated NLRP3 inflammasome/stress granule signalling in macrophages and its correlation with plaque vulnerability: an in vivo and in vitro study

Cited by 31 publications

References 24 publications

Activation of macrophage TBK1‐HIF‐1α‐mediated IL‐17/IL‐10 signaling by hyperglycemia aggravates the complexity of coronary atherosclerosis: An in vivo and in vitro study

Activation of macrophage TBK1‐HIF‐1α‐mediated IL‐17/IL‐10 signaling by hyperglycemia aggravates the complexity of coronary atherosclerosis: An in vivo and in vitro study

Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm

Cerebral-Cardiac Syndrome and Diabetes: Cardiac Damage After Ischemic Stroke in Diabetic State

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