scholarly journals Silence of NLRP3 Suppresses Atherosclerosis and Stabilizes Plaques in Apolipoprotein E-Deficient Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Fei Zheng ◽  
Shanshan Xing ◽  
Zushun Gong ◽  
Wei Mu ◽  
Qichong Xing
Keyword(s):  
Rna Interference ◽  
Apolipoprotein E ◽  
Nlrp3 Inflammasome ◽  
Vital Role ◽  
Nlrp3 Gene ◽  
New Strategy ◽  
Nlrp3 Inflammasomes ◽  
The Impact ◽  
Deficient Mice

Objectives. The role of the NLRP3 inflammasome in atherosclerosis remains controversial. The aim of this study was to determine whether inhibition of NLRP3 signaling by lentivirus-mediated RNA interference could reduce atherosclerosis and stabilizes plaques. We also tried to explore the mechanisms of the impact of NLRP3 inflammasome on atherosclerosis.Methods. Apolipoprotein E-deficient mice aged 8 weeks were fed a high-fat diet and were injected with NLRP3 interfering or mock viral suspension after 4 weeks. Lentivirus transfer was repeated in 2 weeks. Four weeks after the first lentivirus injection, we evaluated the effects of NLRP3 gene silencing on plaque composition and stability and on cholesterol efflux and collagen metabolism, by histopathologic analyses and real-time PCR.Results. Gene silence of NLRP3 prevented plaques progression and inhibited inductions of proinflammatory cytokines. Moreover, this RNA interference reduced plaque content of macrophages and lipid, and increased plaque content of smooth muscle cells and collagen, leading to the stabilizing of atherosclerotic plaques.Conclusions. NLRP3 inflammasomes may play a vital role in atherosclerosis, and lentivirus-mediated NLRP3 silencing would be a new strategy to inhibit plaques progression and to reduce local inflammation.

scholarly journals NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease

2021 ◽  
Vol 22 (21) ◽  
pp. 11588
Author(s):  
Yulia K. Komleva ◽  
Ilia V. Potapenko ◽  
Olga L. Lopatina ◽  
Yana V. Gorina ◽  
Anatoly Chernykh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Nlrp3 Gene ◽  
Brain Insulin ◽  
Nlrp3 Inflammasomes ◽  
The Impact

Background: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. In recent years, attention of researchers has increasingly been focused on studying the role of brain insulin resistance (BIR) in the AD pathogenesis. Neuroinflammation makes a significant contribution to the BIR due to the activation of NLRP3 inflammasome. This study was devoted to the understanding of the potential therapeutic roles of the NLRP3 inflammasome in neurodegeneration occurring concomitant with BIR and its contribution to the progression of emotional disorders. Methods: To test the impact of innate immune signaling on the changes induced by Aβ1-42 injection, we analyzed animals carrying a genetic deletion of the Nlrp3 gene. Thus, we studied the role of NLRP3 inflammasomes in health and neurodegeneration in maintaining brain insulin signaling using behavioral, electrophysiological approaches, immunohistochemistry, ELISA and real-time PCR. Results: We revealed that NLRP3 inflammasomes are required for insulin-dependent glucose transport in the brain and memory consolidation. Conclusions NLRP3 knockout protects mice against the development of BIR: Taken together, our data reveal the protective role of Nlrp3 deletion in the regulation of fear memory and the development of Aβ-induced insulin resistance, providing a novel target for the clinical treatment of this disorder.

Abstract 12527: Serum Amyloid A, Inflammasome Activation and Stroke

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mark S Kindy
Keyword(s):  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Serum Amyloid A ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Stroke Outcomes ◽  
Amyloid A ◽  
The Impact ◽  
Deficient Mice

Serum amyloid A (SAA) proteins are critical to the regulation of inflammation in systemic as well as neurological diseases. Studies have shown that during an acute phase response (APR), SAA levels increase 1000-fold and can stimulate the inflammasome, trigger the recruitment of immune cells to inflammatory sites, and elicit the induction of enzymes that degrade extracellular matrix. Our long-term goal is to dissect the mechanisms regulating SAA function, particularly the contribution to stroke related damage. Recent studies have demonstrated that activation of the inflammasome is a critical event in stroke progression in mice. The central hypothesis is that SAA activates the NLRP3 inflammasome, and amplifying the local inflammatory responses that enhance neuronal cell death and stroke progression. We show that activation of the NLRP3 inflammasome by SAA exacerbates stroke in mice. Using mice deficient in SAA, RAGE and various inflammasome components (cathepsin B, NLRP3, ASC, caspase-1 and IL-1beta) or IL-1R mice, we demonstrated that SAA-mediated stroke outcomes are dependent on the NLRP3 inflammasome. In addition, using microglial cell cultures, we determined the impact of SAA on RAGE mediated pathologies (ROS generation, etc.) as well as the influence of SAA-HDL on SAA-mediated NLRP3 activation. We tested the hypothesis that systemic SAA exacerbates the progression of neuronal cell death and inflammation in stroke. We showed that SAA deficient mice determined the impact on stroke infarct volume and outcomes. In addition, using viral vectors to express SAA as well as an inducible transgene help us determine the role of SAA with specific expression of SAA. The impact of SAA on inflammation, neuronal cell death, matrix remodeling, etc. was attenuated in SAA deficient mice. In addition, we demonstrated the role of SAA and the inflammasome in human stroke, and the relationship between plasma SAA, IL-1beta and the impact on stroke outcomes.

Understanding the role of Inflammasome in Angina Pectoris

2020 ◽  
Vol 21 ◽  
Author(s):  
Ishita Sharma ◽  
Tapan Behl ◽  
Simona Bungau ◽  
Monika Sachdeva ◽  
Arun Kumar ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Angina Pectoris ◽  
Nlrp3 Inflammasome ◽  
Vital Role ◽  
Death Process ◽  
Cell Death Process ◽  
Artery Disease ◽  
Species Production ◽  
Pro Inflammatory Cytokines

Abstract:: Angina pectoris, associated with coronary artery disease, a cardiovascular disease where, pain is caused by adverse oxygen supply in myocardium, resulting in contractility and discomfort in chest. Inflammasomes, triggered by stimuli due to infection and cellular stress have identified to play a vital role in the progression of cardiovascular disorders and thus, causing various symptoms like angina pectoris. Nlrp3 inflammasome, a key contributor in the pathogenesis of angina pectoris, requires activation and primary signaling for the commencement of inflammation. Nlrp3 inflammasome elicit out an inflammatory response by emission of pro inflammatory cytokines by ROS (reactive oxygen species) production, mobilization of K+ efflux and Ca2+ and by activation of lysosome destabilization that eventually causes pyroptosis, a programmed cell death process. Thus, inflammasome are considered to be one of the factors involved in the progression of coronary artery diseases and have an intricate role in development of angina pectoris.

scholarly journals Amelioration of atherosclerosis in apolipoprotein E-deficient mice by combined RNA interference of lipoprotein-associated phospholipase A2 and YKL-40

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0202797 ◽  
Author(s):  
Hui Zhang ◽  
Wenping Zhou ◽  
Chang Cao ◽  
Wenjing Zhang ◽  
Gangqiong Liu ◽  
...  
Keyword(s):  
Rna Interference ◽  
Phospholipase A2 ◽  
Apolipoprotein E ◽  
Deficient Mice

The Role Of Social Networking Between Knowledge Donating And Productivity Among Service Sector Employees

2021 ◽  
Vol 3 (1) ◽  
pp. 1-21
Author(s):  
Sarah Khan ◽  
Dr. Nasir Mehmood
Keyword(s):  
Social Networking ◽  
Knowledge Sharing ◽  
Structural Equation ◽  
Service Sector ◽  
Business Environment ◽  
Vital Role ◽  
Mediating Role ◽  
Networking Technologies ◽  
The Impact

Purpose: The purpose of this study is to examine the direct impact of knowledge donating behaviour on employees’ productivity and an indirect effect through social networking technologies. Social networking technologies play a vital role in the growth and learning of individuals and organizations in today’s competitive business environment. Recently, advancement in social networking technologies has brought a paradigm shift in the overall business environment and specific operational requirements. This study aimed to investigate the role of social networking (SN) between knowledge donating behaviour (KD) and employees’ productivity (EP). Methodology: For this purpose, data were gathered from targeted respondents belonged to the Universities and Banks located in the Northern Punjab region of Pakistan. Structural Equation Modelling technique using the SmartPLS was carried to statistically analyse the responses. Findings: The results showed that the hypothesized relationship between knowledge sharing behaviour (KSB) and employee’s productivity was significant and positively related, while social networking played a significant mediating role between this relationship. Implications: The findings provided useful insight to the managers and policymakers for planning effective use of social networking technologies to craft knowledge sharing behaviour among employees to create efficiencies and intended outcomes. Originality: The study has uniquely focused merging phenomenon of knowledge sharing behaviour in the service sector of Pakistan, specifically among academic and financial sector by exploring the impact of social networking technologies and provide valuable future direction for researchers to further extend the underlined idea in the wake of current Covid-19 Pandemic.

The AIM2 and NLRP3 inflammasomes trigger IL-1–mediated antitumor effects during radiation

2021 ◽  
Vol 6 (59) ◽  
pp. eabc6998
Author(s):  
Chuanhui Han ◽  
Victoria Godfrey ◽  
Zhida Liu ◽  
Yanfei Han ◽  
Longchao Liu ◽  
...  
Keyword(s):  
Antitumor Immunity ◽  
Radiation Treatment ◽  
Wild Type ◽  
Antitumor Effects ◽  
Radiation Induced ◽  
Effects Of Radiation ◽  
Nlrp3 Inflammasomes ◽  
Priming Activity ◽  
Deficient Mice

The inflammasome promotes inflammation-associated diseases, including cancer, and contributes to the radiation-induced tissue damage. However, the role of inflammasome in radiation-induced antitumor effects is unclear. We observed that tumors transplanted in Casp1−/− mice were resistant to radiation treatment compared with tumors in wild-type (WT) mice. To map out which molecule in the inflammasome pathway contributed to this resistant, we investigated the antitumor effect of radiation in several inflammasome-deficient mice. Tumors grown in either Aim2−/− or Nlrp3−/− mice remained sensitive to radiation, like WT mice, whereas Aim2−/−Nlrp3−/− mice showed radioresistance. Mechanistically, extracellular vesicles (EVs) and EV-free supernatant derived from irradiated tumors activated both Aim2 and Nlrp3 inflammasomes in macrophages, leading to the production of interleukin-1β (IL-1β). IL-1β treatment helped overcome the radioresistance of tumors growing in Casp1−/− and Aim2−/−Nlrp3−/− mice. IL-1 signaling in dendritic cells (DCs) promoted radiation-induced antitumor immunity by enhancing the cross-priming activity of DCs. Overall, we demonstrated that radiation-induced activation of the AIM2 and NLRP3 inflammasomes coordinate to induce some of the antitumor effects of radiation by triggering IL-1 signaling in DCs, leading to their activation and cross-priming.

Abstract 152: Stat4 Deficiency limits the Development and Progression of Atherosclerosis

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Paresa Taghavie-Moghadam ◽  
Matthew Butcher ◽  
Mark Kaplan ◽  
Jerry Nadler ◽  
Elena Galkina
Keyword(s):  
T Cells ◽  
B Cell ◽  
Plaque Burden ◽  
Chow Diet ◽  
Th1 Cells ◽  
Peripheral Tissues ◽  
The Impact ◽  
Deficient Mice

T helper 1 (Th1) cells constitute the majority of plaque infiltrating IFNγ+ T cells and play a pro-atherogenic role. Th1 cells are induced via IFNγ-dependent activation of T-box expressed in T cells (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (Stat4). While the role of Tbet in atherosclerosis is established, the impact of the IL-12/Stat4-dependent pathway is not well defined. To address the role of Stat4 in atherosclerosis, we bred Stat4-deficient mice with Apolipoprotein E-deficient mice to generate Stat4-/-Apoe-/- mice. Deficiency of Stat4 resulted in approximately a 70% reduction in the plaque burden for 34 week old Stat4-/-Apoe-/- mice fed a chow diet and in 12 week old Stat4-/-Apoe-/- mice fed a western diet there was approximately a 40% reduction in plaque burden, both compared with diet matched Apoe-/- controls females (p<0.001). To assess the effect of Stat4 on Th1 and Treg cell differentiation, we performed an in vitro polarization assay. Deficiency of Stat4 reduced differentiation of IFNγ+ Th1 cells in Th1 conditions, but supported the induction of Tregs in Treg polarizing conditions, confirming the importance of Stat4 in regulating the Th1/Treg balance. In contrast to the in vitro results, we found no difference in the expression of both IFNγ and Foxp3 amongst Stat4-/-Apoe-/- and Apoe-/- lymph nodes and splenic CD4+ T cells; suggesting that additional cytokines in vivo may induce IFNγ+Th1 and inhibit Treg differentiation. Stat4 deficiency also resulted in increased splenic B cell numbers and a slight increase in B1a dependent T15/E06 mRNA expression. Stat4 is a powerful regulator of chemokine expression within peripheral tissues. Adoptively transferred Apoe-/- B cells and CD11b+ cells migrated more efficiently into Stat4-/-Apoe-/- aortas compared to Apoe-/- recipients. However, percentages of macrophages, as determined by CD11b+CD68+ were reduced within the spleens and aortas of Stat4-/-Apoe-/- mice as compared to Apoe-/- controls at steady state conditions. In conclusion, Stat4 deficiency results in reduced atherosclerosis via the modulation of B cell function and aortic leukocyte content.

scholarly journals Chronic iron overload intensifies atherosclerosis in apolipoprotein E deficient mice: Role of oxidative stress and endothelial dysfunction

Life Sciences ◽  
2019 ◽  
Vol 233 ◽  
pp. 116702 ◽  
Author(s):  
Vinícius Bermond Marques ◽  
Marcos André Soares Leal ◽  
Jandinay Gonzaga Alexandre Mageski ◽  
Helbert Gabriel Fidelis ◽  
Breno Valentim Nogueira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Iron Overload ◽  
Apolipoprotein E ◽  
Deficient Mice
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