Macrophage–NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes

Lin, Hong-Bin; Wei, Guanshan; Li, Fengxian; Guo, Wenjing; Peng, Hong; Weng, Yaqian; Zhang, Qianqian; Xu, Shiyuan; Liang, Wenbin; Zhang, You; Zhang, Hongfei

doi:10.1007/s12264-020-00544-0

Cited by 31 publications

(26 citation statements)

References 46 publications

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“…The type 2 diabetic mouse model was generated as described previously (Lin et al, 2020 ). Briefly, we first fed each mouse on a high-fat diet (Guangdong Medical Laboratory Animal Center, Guangzhou, China) for 3 w. A dose of 100 mg/kg streptozotocin (STZ, Sigma, St. Louis, MO, USA) was then injected intraperitoneally.…”

Section: Methodsmentioning

confidence: 99%

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NLRP3 Inflammasome: A Potential Target in Isoflurane Pretreatment Alleviates Stroke-Induced Retinal Injury in Diabetes

Lin

Ying-hui

Zhang

et al. 2021

Front. Cell. Neurosci.

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Ischemic stroke remains a devastating disease which is the leading cause of death worldwide. Visual impairment after stroke is a common complication which may lead to vision loss, greatly impacting life quality of patients. While ischemic stroke is traditionally characterized by a blockage of blood flow to the brain, this may coincide with reduced blood flow to the eye, resulting in retinal ischemia and leading to visual impairment. Diabetes increases the risk of ischemic stroke and induces diabetic retinopathy; the latter may be more sensitive to the ischemic retinal injury. In diabetic status, the underlying mechanism in stroke-induced retinal injury has not been fully clarified. The NLR pyrin domain containing 3 (NLRP3) inflammasome is an important activator of inflammation, which may play a critical role in catalyzing and forming certain pro-inflammatory cytokines in both cerebral and retinal ischemia. Isoflurane has been demonstrated to inhibit the activation of the NLRP3 inflammasome and show neuroprotective effects. In this study, we established a diabetic mouse model and performed the middle cerebral artery occlusion procedure to induce ischemic stroke. Our results revealed that cerebral ischemia-induced retinal injury in the diabetic model. Isoflurane pretreatment alleviated the cerebral and retinal injury after ischemic stroke. Of note, isoflurane pretreatment inhibited the NLRP3 inflammasome activation in the retina, indicating that isoflurane pretreatment may provide substantial retinal protection in stroke-induced retinal injury in diabetes.

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Section: Methodsmentioning

confidence: 99%

“…The ischemic stroke mouse model was generated by MCAO following the protocol of our previous study (Lin et al, 2020 ). In brief, mice were anesthetized with 2% isoflurane (RWD Life Science Co., Ltd, Shenzhen, China).…”

Section: Methodsmentioning

confidence: 99%

NLRP3 Inflammasome: A Potential Target in Isoflurane Pretreatment Alleviates Stroke-Induced Retinal Injury in Diabetes

Lin

Ying-hui

Zhang

et al. 2021

Front. Cell. Neurosci.

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“…A recently developed NLRP3 inhibitor, CY-09, binds directly to the ATP-binding motif of the NACHT domain, thus inhibiting NLRP3 assembly and ATPase activity. Its therapeutic efficacy has been tested on animal models of CAPS and type 2 diabetes [ 117 ]. The use of CY-09 in a mouse model of diabetic stroke was able to protect from cardiac dysfunction associated with diabetic ischemic stroke [ 118 ].…”

Section: Nlrp3 Inflammasome As a Target For Pharmacological Inhibimentioning

confidence: 99%

NLRP3 Inflammasome Inhibitors in Cardiovascular Diseases

2021

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Virtually all types of cardiovascular diseases are associated with pathological activation of the innate immune system. The NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is a protein complex that functions as a platform for rapid induction of the inflammatory response to infection or sterile injury. NLRP3 is an intracellular sensor that is sensitive to danger signals, such as ischemia and extracellular or intracellular alarmins during tissue injury. The NLRP3 inflammasome is regulated by the presence of damage-associated molecular patterns and initiates or amplifies inflammatory response through the production of interleukin-1β (IL-1β) and/or IL-18. NLRP3 activation regulates cell survival through the activity of caspase-1 and gasdermin-D. The development of NLRP3 inflammasome inhibitors has opened the possibility to targeting the deleterious effects of NLRP3. Here, we examine the scientific evidence supporting a role for NLRP3 and the effects of inhibitors in cardiovascular diseases.

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“…Diabetes increases the incidence of cardiac complications after IS, which manifest as myocardial infarction, congestive heart failure (85), arrhythmia, cardiac arrest (16), and exacerbate mortality and worse neural prognosis in the post-stroke state (15,49,86). Burkot et al have reported that heart failure occurrence rate after IS is 22.3% in diabetic patients and 15.1% without diabetes (10).…”

Section: Diabetic Status Exacerbates Cerebral-cardiac Syndrome Clinical Evidencementioning

confidence: 99%

“…Inflammation is an important trigger for both diabetes and CCS (11,12), and NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is the crucial element to promote the maturation and release of IL-1b and IL-18 (13). Recent studies have indicated the role of NLRP3 inflammasome in diabetes and diabetic CCS (14,15). Therefore, the responsible pathway of NLRP3 inflammasome activation and subsequent effects on diabetic CCS need further exploration.…”

Section: Introductionmentioning

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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Macrophage–NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes

Cited by 31 publications

References 46 publications

NLRP3 Inflammasome: A Potential Target in Isoflurane Pretreatment Alleviates Stroke-Induced Retinal Injury in Diabetes

NLRP3 Inflammasome: A Potential Target in Isoflurane Pretreatment Alleviates Stroke-Induced Retinal Injury in Diabetes

NLRP3 Inflammasome Inhibitors in Cardiovascular Diseases

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

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