NLRP3: A Novel Mediator in Cardiovascular Disease

Zhou, Wenyi; Chen, Chun-Yuan; Chen, Zhiheng; Liu, Lin; Jiang, Jie; Wu, Zhixiang; Zhao, Mingyi; Chen, Yanfang

doi:10.1155/2018/5702103

Cited by 135 publications

(110 citation statements)

References 60 publications

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“…Multiple molecular mechanisms have been proposed to result in the development of DCM including myocardial inflammation, fibrosis, cardiomyocyte oxidative stress, apoptosis, autophagy, mitochondrial dysfunction and so on [4]. In addition, the NOD-like receptor 3 (NLRP3) inflammasome-induced pyroptosis, a novel programmed cell death process, is increasingly recognized in cardiovascular disease including DCM [5]. Caspase1 is activated by ligands of NLRP3 inflammasome, which further triggers the cleavage of pro-inflammatory cytokinesis such as interleukin-1β, 18 (IL-1β, and gasdermin D (GSDMD).…”

Section: Introductionmentioning

confidence: 99%

Empagliflozin prevents cardiomyopathy via sGC-cGMP-PKG pathway in type 2 diabetes mice

Xue

Wang

et al. 2019

Clinical Science

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Cardiovascular complications contribute to the major mortality and morbidity in type 2 diabetes. Diabetic cardiomyopathy (DCM) is increasingly recognized as an important cause of heart failure. EMPA-REG OUTCOME trial has reported that empagliflozin, the sodium-glucose cotransporter 2 inhibitor, exerts cardiovascular benefits on diabetic population. However, the mechanism by which empagliflozin alleviates DCM still remains unclear. In the current study, we investigated the cardiac protective effects of empagliflozin on spontaneous type 2 diabetic db/db mice and its potential mechanism. Eight weeks of empagliflozin treatment (10 mg/kg/day) decreased body weight and blood glucose level, and increased urinary glucose excretion (UGE) in diabetic mice. Echocardiography revealed that both systolic and diastolic functions of db/db mice were also obviously improved by empagliflozin. Furthermore, empagliflozin-treated diabetic mice presented with amelioration of cardiac hypertrophy and fibrosis. In addition, diabetic hearts exhibited the deterioration of oxidative stress, apoptosis and pyroptosis, while these effects were significantly counteracted after empagliflozin treatment. Moreover, empagliflozin rescued diabetes-induced suppression of sGC (soluble guanylate cyclase enzyme)-cGMP (cyclic guanosine monophosphate)-PKG (cGMP-dependent protein kinase) pathway. However, when sGC-β expression of hearts was inhibited by transvascular delivery of small interfering RNA, cardiac dysfunction was aggravated and the advantages of empagliflozin were reversed through inhibiting sGC-cGMP-PKG pathway. Collectively, these findings indicate that empagliflozin improves cardiac function involving the inhibition of oxidative stress-induced injury via sGC-cGMP-PKG pathway and may be a promising therapeutic option for DCM.

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Section: Introductionmentioning

confidence: 99%

Empagliflozin prevents cardiomyopathy via sGC-cGMP-PKG pathway in type 2 diabetes mice

Xue

Wang

et al. 2019

Clinical Science

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“…Targeting against the assembly and activity of the NLRP3 inflammasome is a potential and novel therapy for inflammasome-associated diseases, especially for cardiovascular diseases [55][56][57][58][59][60]. Some studies have indicated that blocking S194 phosphorylation can prevent NLRP3 inflammasome activation.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 Inflammasome and Its Central Role in the Cardiovascular Diseases

Tong

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background/Aims. NLRP3 inflammasome, an inflammasome which consists of nucleotide-binding oligomerization domain- (Nod-) like receptor3 (NLRP3) scaffold, apoptosis-associated speck-like protein (ASC) containing a CARD adaptor, and pro-caspase-1, is assembled after the cytoplasmic leucine-rich repeats (LRRs) of NLRP3 sense pathogens or danger signals. In recent years, the role of inflammasome in cardiovascular diseases has attracted mounting attention, and the in-depth study of its mechanism is gradually clear. Materials. The NLRP3 inflammasome controls the activation of the proteolytic enzyme caspase-1. Caspase-1 in turn regulates the maturation of the proinflammasome cytokines IL-1β and IL-18, which leads to an inflammatory response. We made a mini-review on the association of regulatory mechanisms of NLRP3 inflammasome with the development of cardiovascular diseases systematically based on the recent research studies. Discussion. The inflammasome plays an indispensable role in the development of atherosclerosis, coronary heart diseases (CHD), and heart ischemia-reperfusion (I/R) injury, and NLRP3 inflammasome may become a new target for the prevention and treatment of cardiovascular diseases. Effective regulation of NLRP3 may help prevent or even treat cardiovascular diseases. Conclusion. This mini-review focuses on the association of regulatory mechanisms of NLRP3 inflammasome with the development of cardiovascular diseases, which may supply some important clues for future therapies and novel drug targets for cardiovascular diseases.

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“…IL, interleukin; IFN, interferon; NO, nitric oxide; TLR, toll-like receptors; TNF, tumor necrosis factor; ROS, reactive oxygen species; mt-DNA, mitochondrial DNA; mt-ROS, mitochondrial reactive oxygen species Therapies associ ated with blocking the NLRP3 inflammasome have yielded promising results. An example of this, as previously mentioned, is the glyburide analog, 16673-34-0, that has shown benefits in ischemia-reperfusion animal models [63,64,98]. Although no clinical trials are being conducted to target NLRP3 directly, IL-1β, a byproduct resulting from NLRP3 activation, has revealed beneficial outcomes associated to inflammation resolution in both HFrEF and HFpEF.…”

Section: The Heart As a Target Of Systemic Inflammationmentioning

confidence: 99%

What Is the Role of the Inflammation in the Pathogenesis of Heart Failure?

et al. 2020

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Purpose of Review In heart failure, whether it is associated with reduced or preserved ejection fraction, the immune system is activated and contributes to heart remodeling and impaired function. Recent Findings Studies indicate that cells of the immune system not only play a role in the pathology but are also critical regulators of heart function. Knowledge about the role of the immune system driving heart failure will lead to the development of new targets to this system, particularly in those patients that, despite the apparent wellness, relapse and worsen. Summary In this review, we will address the diverse mechanisms that trigger inflammation and their impact on heart failure progression.

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NLRP3: A Novel Mediator in Cardiovascular Disease

Cited by 135 publications

References 60 publications

Empagliflozin prevents cardiomyopathy via sGC-cGMP-PKG pathway in type 2 diabetes mice

Empagliflozin prevents cardiomyopathy via sGC-cGMP-PKG pathway in type 2 diabetes mice

NLRP3 Inflammasome and Its Central Role in the Cardiovascular Diseases

What Is the Role of the Inflammation in the Pathogenesis of Heart Failure?

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