Statins ameliorate cholesterol-induced inflammation and improve AQP2 expression by inhibiting NLRP3 activation in the kidney

Kong, Yonglun; Feng, Weijing; Zhao, Xueyan; Zhang, Puhua; Li, Suchun; Z, Li; Lin, Yanwei; Liang, Boen; Li, Chunling; Wang, Weidong; Huang, Hui

doi:10.7150/thno.49603

Cited by 33 publications

(25 citation statements)

References 53 publications

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“…mRNA was reversely transcribed to cDNA using the cDNA kit (Takara). cDNA was amplified in a mixture reaction system containing SYBR Green qPCR SuperMix-UDG (Takara) and specific primer sequences ( Table S1 ) [ 48 ]. qRT-PCR analysis was performed using ABI 7900HT platform (Applied Biosystems, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss

Dai

et al. 2021

Bioactive Materials

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Introduction Magnesium (Mg) has a prophylactic potential against the onset of hyperlipidemia. Similar to statin, Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass. The combination of statin with Mg ions (Mg 2+ ) may be able to alleviate the high-fat diet (HFD)-induced bone loss and reduce the side-effects of statin. This study aimed to explore the feasibility of combined Mg 2+ with simvastatin (SIM) for treating HFD-induced bone loss in mice and the involving mechanisms. Materials and methods C57BL/6 male mice were fed with a HFD or a normal-fat diet (NFD). Mice were intraperitoneally injected SIM and/or orally received water with additional Mg 2+ until sacrificed. Enzyme-linked immunosorbent assay was performed to measure cytokines and cholesterol in serum and liver lysates. Bone mineral density (BMD) and microarchitecture were assessed by micro-computed tomography (μCT) in different groups. The adipogenesis in palmitate pre-treated HepG2 cells was performed under various treatments. Results μCT analysis showed that the trabecular bone mass was significantly lower in the HFD-fed group than that in NFD-fed group since week 8. The cortical thickness in HFD-fed group had a significant decrease at week 24, as compared with NFD-fed group. The combination of Mg 2+ and SIM significantly attenuated the trabecular bone loss in HFD-fed mice via arresting the osteoclast formation and bone resorption. Besides, such combination also reduced the hepatocytic synthesis of cholesterol and inhibited matrix metallopeptidase 13 ( Mmp13 ) mRNA expression in pre-osteoclasts. Conclusions The combination of Mg 2+ and SIM shows a synergistic effect on attenuating the HFD-induced bone loss. Our current formulation may be a cost-effective alternative treatment to be indicated for obesity-related bone loss.

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Section: Methodsmentioning

confidence: 99%

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss

Dai

et al. 2021

Bioactive Materials

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“…Considering that the contribution of the NLRP3 inflammasome varies among different cardiac cells, the effects of RVS on the NLRP3 inflammasome may also differ. While majority previous studies focused on the inflammation suppression effect of RVS via inhibiting the NLRP3 inflammasome 43 – 45 , relatively little is known about the anti-pyroptosis role of RVS, especially in cardiomyocytes. In our study, RVS treatment suppressed the expression of cleaved-caspase-1 and IL-1β, as well as GSDMD-N, implying the inhibitory role of RVS in the NLRP3 inflammasome pathway.…”

Section: Discussionmentioning

confidence: 99%

Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation

Chen

Zhou

et al. 2021

Cell Death Dis

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Coronary microembolization (CME), a common reason for periprocedural myocardial infarction (PMI), bears very important prognostic implications. However, the molecular mechanisms related to CME remain largely elusive. Statins have been shown to prevent PMI, but the underlying mechanism has not been identified. Here, we examine whether the NLRP3 inflammasome contributes to CME-induced cardiac injury and investigate the effects of statin therapy on CME. In vivo study, mice with CME were treated with 40 mg/kg/d rosuvastatin (RVS) orally or a selective NLRP3 inflammasome inhibitor MCC950 intraperitoneally (20 mg/kg/d). Mice treated with MCC950 and RVS showed improved cardiac contractile function and morphological changes, diminished fibrosis and microinfarct size, and reduced serum lactate dehydrogenase (LDH) level. Mechanistically, RVS decreased the expression of NLRP3, caspase-1, interleukin-1β, and Gasdermin D N-terminal domains. Proteomics analysis revealed that RVS restored the energy metabolism and oxidative phosphorylation in CME. Furthermore, reduced reactive oxygen species (ROS) level and alleviated mitochondrial damage were observed in RVS-treated mice. In vitro study, RVS inhibited the activation of NLRP3 inflammasome induced by tumor necrosis factor α plus hypoxia in H9c2 cells. Meanwhile, the pyroptosis was also suppressed by RVS, indicated by the increased cell viability, decreased LDH and propidium iodide uptake in H9c2 cells. RVS also reduced the level of mitochondrial ROS generation in vitro. Our results indicate the NLRP3 inflammasome-dependent cardiac pyroptosis plays an important role in CME-induced cardiac injury and its inhibitor exerts cardioprotective effect following CME. We also uncover the anti-pyroptosis role of RVS in CME, which is associated with regulating mitochondrial ROS.

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“…These PRRs recognize different PAMPs and DAMPs. Among them, NLRP3 is most frequently investigated and has the most diverse activators 3 , 6 , 30 , 40 , 41 . Unlike other PRRs, NLRP3 and pyrin can be activated without a direct contact with their activators.…”

Section: Inflammasome Complex Formation and Activationmentioning

confidence: 99%

Exosome-inflammasome crosstalk and their roles in inflammatory responses

2021

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Inflammasome is a complex of multiple proteins found in cytoplasm of the cells activated by infectious and/or non-infectious stimuli. This complex involves caspase-1 activation, leading to unconventional secretion of interleukin-1β (IL-1β) and IL-18 and inflammatory cascade. Exosome is the nanoscale membrane-bound extracellular vesicle that plays significant roles in intercellular communications by carrying bioactive molecules, e.g., proteins, RNAs, microRNAs (miRNAs), DNAs, from one cell to the others. In this review, we provide the update information on the crosstalk between exosome and inflammasome and their roles in inflammatory responses. The effects of inflammasome activation on exosomal secretion are summarized. On the other hand, the (dual) effects of exosomes on inhibiting and promoting inflammasome activation are discussed. Finally, perspectives on therapeutic roles of exosomes in human diseases and future direction of the research on exosome-inflammasome crosstalk are provided.

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Statins ameliorate cholesterol-induced inflammation and improve AQP2 expression by inhibiting NLRP3 activation in the kidney

Cited by 33 publications

References 53 publications

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss

Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation

Exosome-inflammasome crosstalk and their roles in inflammatory responses

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