Targeted delivery of anti-inflammatory cytokine by nanocarrier reduces atherosclerosis in Apo E−/- mice

Kim, Manse; Sahu, Abhishek; Hwang, Youngmin; Kim, Jun Seok; Nam, Gi Hoon; Kim, In San; Kwon, Ick Chan; Tae, Giyoong

doi:10.1016/j.biomaterials.2019.119550

Cited by 90 publications

(66 citation statements)

References 53 publications

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“…Statins are widely orally prescribed serum LDL cholesterol-lowering drugs, raising the expression of LDL receptor in hepatocytes [6]. Clinical data has shown that orally administered statins can reduce the risk of cardiovascular disease (CVD) and attenuate the development of atherosclerotic plaques [7]. Statins exhibit pleiotropic properties via reductase derived metabolites blockade, including antioxidant effects, anti-inflammatory effects and multiple vasculoprotective effects on endothelial cells, vascular smooth muscle cells and monocytes [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis

et al. 2020

J Nanobiotechnol

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Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the cellular uptake experiment demonstrated that SIM-loaded HA-coated micelles can be effectively internalized by LPS-induced RAW264.7 cells and showed high cytotoxicity against the cells, but low cytotoxicity against LO2 cells. In mouse models of atherosclerosis, intravenously SIM-loaded HA-coated micelles can effectively reduce plaque content of cholesterol, resulting in remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system provides a promising and innovative option against atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis

et al. 2020

J Nanobiotechnol

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“…Mox macrophages, rich in advanced mouse lesions, play an atheroprotective role because the low-density lipoprotein receptor-deficient mice would emerge with accelerated atherogenesis which results from myeloid deficiency of Nrf2 [25]. Additionally, some inflammatory genes have upregulated expression in Mox macrophages in keeping with macrophages which respond to oxidized phospholipids by upregulation of inflammatory gene expression in wild-type mice [26].…”

Section: Macrophages In the Progression Stagementioning

confidence: 99%

“…Anti-inflammatory M2-type macrophages were identified in the stable plaque areas with small possibility to form foam cells. Therefore, the plaque progression can be reflected by proinflammatory and anti-inflammatory macrophage subtypes [26]. Transcriptome-based network analysis is a powerful modern tool for studying macrophage activation and function, providing a set of data on specific genes involved in different stages of macrophage activation [64].…”

Section: Inducing Macrophage Polarizationmentioning

confidence: 99%

Macrophage-Based Therapies for Atherosclerosis Management

Peng

Jin

et al. 2020

Journal of Immunology Research

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Atherosclerosis (AS), a typical chronic inflammatory vascular disease, is the main pathological basis of ischemic cardio/cerebrovascular disease (CVD). Long-term administration was characterized with low efficacy and serious side effects, while the macrophages with attractive intrinsic homing target have great potential in the efficient and safe management of AS. In this review, we focused on the systematical summary of the macrophage-based therapies in AS management, including macrophage autophagy, polarization, targeted delivery, microenvironment-triggered drug release, and macrophage- or macrophage membrane-based drug carrier. In conclusion, macrophage-based therapies have great promise to effectively manage AS in future research and clinic translation.

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“…AG regulated SREBP and other metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower lipid levels and enhanced insulin sensitivity in mice with high fat diet (HFD)-induced obesity (21). Decrease of pathological lesions contain AS and NAFLD in ApoE knockout (ApoE -/-) mice with HFD can be controlled by regulating the lipid metabolism and inflammatory (22). We tried to intervene it by AG to analyze the information from gut microbes.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

Shi

et al. 2020

Preprint

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Mechanisms relating the gut bacteria to Nonalcoholic Fatty Liver Disease (NAFLD) have been proposed containing the dysbiosis-induced dysregulation of hepatic lipid metabolism that allows for the translocation of microbial components and leads to hepatic inflammation and steatosis. Andrographolide (AG) regulates inflammation mediated by NF-κB pathway which also play a key role in reduction of inflammation and fibrosis in experimental nonalcoholic steatohepatitis (NASH), yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that ApoE knockout (Apoe -/-) mice fed a high-fat diet (HFD) supplemented with AG regulates levels of biochemical index and inflammatory cytokines associated with gut microbe. Moreover, HEPG2 cells induced by ox-LDL were used as validation in vitro. H&E staining and Oil-Red staining were respectively used for tissue and cells morphology. Gut microbiota were examined by 16S rRNA sequencing. Expression of NF-κB, C/EBPβ and PPAR-γ in liver and HEPG2 cells were detected by western blot and qRT-PCR. The results showed, among others, that AG alleviate hepatic steatosis and fat content in HEPG2 cells, while it induced decreased levels of Bacteroides, and increased levels of Faecalibaculum, Akkermansia. We further identified that inhibition of NF-κB/C/EBPβ/PPAR-γ pathway of hepatic steatosis model in vivo and vitro by AG also contributes to prevention of HFD-induced inflammation and dislipidemia. Importantly, as result of pearson correlation, Bacteroides may be the most relevant one fundamentally involved in the mechanism of AG attenuates NAFLD. Together, our findings uncover an interaction between AG and gut microbiota as a novel mechanism for the anti-NAFLD effect of AG acting through prevention of microbial dysbiosis, dislipidemia and inflammation.Importance HFD due to gut microbial dysbiosis is a major contributor to the pathogenesis of dislipidemia and inflammation, which primarily mediates the development of NAFLD. A treatment strategy to reduce both dislipidemia and inflammation appears to be an effective approach for addressing the issue of NAFLD. Andrographolide (AG) is the major effect component in traditional Chinese medicine Chuan-xin-lian (Andrographis). Little is known about the role of gut microbiota in the anti-NAFLD effect of AG. 16S rRNA gene sequencing revealed that AG significantly decreased Bacteroides and increased Faecalibaculum, Akkermansia. By using vivo and vitro experiment, we prove that gut microbiota plays a key role in AG-induced protective against high-fat-diet-induced dislipidemia and inflammation. Moreover, NF-κB/C/EBPβ/PPAR-γ pathway inhibition was partially involved in the beneficial effect of AG. Together, these data suggest that the gut microbiome is a critical factor for the anti-NAFLD effects of AG.

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Targeted delivery of anti-inflammatory cytokine by nanocarrier reduces atherosclerosis in Apo E−/- mice

Cited by 90 publications

References 53 publications

Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis

Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis

Macrophage-Based Therapies for Atherosclerosis Management

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

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