JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-22
·
IF 10.2
Zhu Li,Li Hongjiao,Li Jiyu,Zhong Yuan,Wu Shuai,Yan Meng,Ni Sheng,Zhang Kun,Wang Guixue,Qu Kai,Yang Deqin,Qin Xian,Wu Wei
A disorder of cholesterol homeostasis is one of the main initiating factors in the progression of atherosclerosis (AS). Metabolism and removal of excess cholesterol facilitates the prevention of foam cell formation. However, the failure of treatment with drugs (e.g. methotrexate, MTX) to effectively regulate progression of disease may be related to the limited drug bioavailability and rapid clearance by immune system. Thus, based on the inflammatory lesion “recruitment” properties of macrophages, MTX nanoparticles (MTX NPs) camouflaged with macrophage membranes (MM@MTX NPs) were constructed for the target to AS plaques. MM@MTX NPs exhibited a uniform hydrodynamic size around ~ 360 nm and controlled drug release properties (~ 72% at 12 h). After the macrophage membranes (MM) functionalized “homing” target delivery to AS plaques, MM@MTX NPs improved the solubility of cholesterol by the functionalized β-cyclodextrin (β-CD) component and significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1, resulting in efficiently inhibiting the formation of foam cells. Furthermore, MM@MTX NPs could significantly reduce the area of plaque, aortic plaque and cholesterol crystals deposition in ApoE−/− mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS.Graphical Abstract
研究领域:
纳米技术
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药学
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心血管疾病
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Yi Zhang,Xiujin Shi,Jialun Han,Wenxing Peng,Zhenwei Fang,Yang Zhou,Xiaoyu Xu,Jie Lin,Fucheng Xiao,Limin Zhao,Yang Lin
Introduction As the primary immune cells, macrophages play a key role in atherosclerotic progression. M2 macrophage polarization has been reported to promote tissue repair and attenuate plaque formation upon the expression of anti-inflammatory factors. Convallatoxin (CNT) is a natural cardiac glycoside with anti-inflammatory pharmacological properties. However, whether CNT protects against atherosclerosis (AS) and underlying mechanisms is unknown. This work was designed to explore the potential effects of CNT on atherosclerosis.Methods In this study, Apolipoprotein E deficiency (ApoE−/-) mice fed with high-fat diet were established, and CNT (50 or 100 μg/kg) were intragastrically administrated for 12 weeks every day. In vitro, RAW264.7 macrophages stimulated with ox-LDL were treated with CNT (50 or 100 nM) for 24 h. The specific PPARγ antagonist, GW9662, was used to block the PPARγ signaling pathway in vitro. Then, the atherosclerotic lesions, macrophage polarization markers, inflammatory cytokines and PPARγ signaling pathway were examined in further examinations.Results Our results showed that the atherosclerotic lesions were reduced by CNT, as demonstrated by the downregulation of serum lipid level and aortic plaque area in AS mice. Furthermore, we found that CNT treatment promoted the expression of M2 macrophage markers (Arg1, Mrc1, Retnla and Chi3l3), and decreased the levels of pro-inflammatory cytokines (IL-6 and TNF-α), accompanied by the increase of anti-inflammatory factor (IL-10) in aortic vessels of AS mice. In ox-LDL-induced RAW264.7 cells, CNT administration also facilitated macrophages polarizing towards M2 subtype and inhibited inflammatory responses. Furthermore, both the in vivo and in vitro experiments showed CNT could increase the expression of PPARγ, Integrin αv and Integrin β5, and GW9662 could block CNT-induced M2 macrophage polarization.Conclusion Taken together, these data suggest that CNT may promote M2 macrophage polarization to exert an anti-atherosclerotic effect, partially through activating PPARγ-Integrin αvβ5 signaling pathway.
研究领域:
心血管疾病
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免疫学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Cui Tang,Hui Wang,Lina Guo,Chan Zou,Jianming Hu,Hanyong Zhang,Wenhu Zhou,Guoping Yang
Atherosclerosis (AS) is a major contributor to cardiovascular diseases, necessitating the development of novel therapeutic strategies to alleviate plaque burden. Macrophage efferocytosis, the process by which macrophages clear apoptotic and foam cells, plays a crucial role in plaque regression. However, this process is impaired in AS lesions due to the overexpression of CD47, which produces a “do not eat me” signal. In this study, we investigated the potential of CpG, a toll-like receptor 9 agonist, to enhance macrophage efferocytosis for AS therapy. We demonstrated that CpG treatment promoted the engulfment of CD47-positive apoptotic cells and foam cells by macrophages. Mechanistically, CpG induced a metabolic shift in macrophages characterized by enhanced fatty acid oxidation and de novo lipid biosynthesis, contributing to its pro-efferocytic effect. To enable in vivo application, we conjugated CpG on silver nanoparticles (AgNPs) to form CpG-AgNPs, which could protect CpG from biological degradation, promote its cellular uptake, and release CpG in response to intracellular glutathione. Combining the intrinsic antioxidative and anti-inflammatory abilities of AgNPs, such nanomedicine displayed multifunctionalities to simultaneously promote macrophage efferocytosis and repolarization. In an ApoE–/– mouse model, intravenous administration of CpG-AgNPs effectively targeted atherosclerotic plaques and exhibited potent therapeutic efficacy with excellent biocompatibility. Our study provides valuable insights into CpG-induced macrophage efferocytosis and highlights the potential of CpG-AgNPs as a promising therapeutic strategy for AS.
研究领域:
纳米医学
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心血管疾病
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2024
·Vol. 14
·期 10
·1226
·
IF 4.8
Wenjuan Quan,Taoli Sun,Bo Hu,Quanye Luo,Yancheng Zhong,Wen Chen,Qinhui Tuo
Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and foam cell formation in the arterial wall. Promoting macrophage autophagy has emerged as a promising therapeutic strategy against atherosclerosis. Dipsacoside B (DB) is an oleanane-type pentacyclic triterpenoid saponin extracted from Lonicerae flos with potential anti-atherosclerotic properties. In this study, we investigated the effects of DB on atherosclerosis progression in ApoE −/− mice fed a high-fat diet and explored the underlying mechanisms in oxidized low-density lipoprotein (ox-LDL)-induced foam cells. DB treatment significantly reduced atherosclerotic lesion size, improved plaque stability, and regulated lipid metabolism without impairing liver and kidney function in ApoE −/− mice. In vitro studies revealed that DB dose-dependently inhibited ox-LDL internalization and intracellular lipid accumulation in RAW264.7 macrophages. Mechanistically, DB induced autophagy, as evidenced by increased autophagosome formation and upregulated expression of autophagy markers LC3-II and p62 both in vivo and in vitro. Inhibition of autophagy by chloroquine abolished the antiatherosclerotic and pro-autophagic effects of DB. Furthermore, DB treatment increased LC3-II and p62 mRNA levels, suggesting transcriptional regulation of autophagy. Collectively, our findings demonstrate that DB exerts anti-atherosclerotic effects by inhibiting foam cell formation via autophagy induction, providing new insights into the pharmacological actions of DB and its potential as a therapeutic agent against atherosclerosis.
研究领域:
心血管疾病
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药理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Pei Lin,Qiqi Wang,Qi Wang,Jiayun Chen,Liangliang He,Zifei Qin,Shaoping Li,Jingyan Han,Xinsheng Yao,Yang Yu,Zhihong Yao
Allium Macrostemon Bge. (AMB) is a well-known homology of herbal medicine and food that has been extensively used for thousands of years to alleviate cardiovascular diseases. It contains a significant amount of polysaccharides, yet limited research exists on whether these polysaccharides are responsible for its cardiovascular protective effects. In this study, the anti-atherosclerosis effect of the crude polysaccharides of AMB (AMBP) was evaluated using ApoE −/− mice fed a high-fat diet, along with ox-LDL-induced Thp-1 foam cells. Subsequently, guided by the inhibitory activity of foam cells formation, a major homogeneous polysaccharide named AMBP80-1a was isolated and purified, yielding 11.1 % from AMB. The molecular weight of AMBP80-1a was determined to be 10.01 kDa. AMBP80-1a was firstly characterized as an agavin-type fructan with main chains consisting of →1)- β - d -Fru f -(2→ and →1,6)- β - d -Fru f -(2→ linked to an internal glucose moiety, with →6)- β - d -Fru f -(2→ and β - d -Fru f -(2→ serving as side chains. Furthermore, the bio-activity results indicated that AMBP80-1a reduced lipid accumulation and cholesterol contents in ox-LDL-induced Thp-1 foam cell. These findings supported the role of AMBP in alleviating atherosclerosis in vivo/vitro . AMBP80-1a, as the predominant homogeneous polysaccharide in AMB, was expected to be developed as a functional agent to prevent atherosclerosis.
研究领域:
药理学
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心血管疾病
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分子生物学
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营养保健品
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2024
·
IF 9.1
Xiaozhi Hu,Yanyang Nan,Yuting Zhang,Jiajun Fan,Hanqi Wang,Yu Bai,Yuanzhen Zhang,Xuyao Zhang,Zeguo Zhu,Zhonglian Cao,Xiaomiao Ye,Tao Wu,Shuwen Xu,Zhengyu Wu,Wei Hu,Dianwen Ju
Atherosclerosis (AS) ultimately cause major adverse cardiovascular events (MACEs). While traditional strategies by lipid-reducing have reduced MACEs, many patients continue to face significant risks. It might attribute to the upregulation of CD47 expression in AS lesions, that mediated anti-efferocytosis of macrophages. Therefore, we propose simultaneously blocking ANGPTL3, a vital regulator of lipid metabolism, and CD47 might be a potential approach for AS therapy. Firstly, we investigate the role of a novel anti-ANGPTL3 nanobody-Fc (FD03) in AS. We found that FD03 treatment significantly decreased circulating lipids, plaque size, and lipid deposition in apoE -/- mice compared to control Ab, but there was a twofold increase in plaque formation in comparison to baseline. However, immunofluorescence indicated the upregulation of CD47 expression in the plaques even after FD03 treatment compared to normal vascular tissue. Next, a bifunctional protein containing signal regulatory protein alpha (SIRPα) and FD03 (SIRPαD1-FD03) was constructed to block CD47 and ANGPTL3 concurrently, which had high purity, robust stability, and high affinity to CD47 and ANGPTL3 with biological activity in vitro . Furthermore, SIRPαD1-FD03 fusion protein exhibited the enhanced therapeutic effect on AS compared with SIRPαD1-Fc or FD03, regressing plaque contents and the necrotic core equal to baseline. Mechanistically, SIRPαD1-FD03 reduced serum lipids, augmented the efferocytosis rate and macrophage M2 polarization, and decreased the reactive oxygen species (ROS) and lipid peroxidation level in atherosclerotic plaques. Collectively, our project suggests an effective approach for AS by simultaneously blocking ANGPTL3 and CD47 to regulate lipid metabolism, macrophage activity and lipid peroxidation.
研究领域:
心血管疾病
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免疫学
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药理学
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分子生物学
✓ 已验证
DOI
高影响因子
Food & Function
·
2023
·Vol. 14
·期 7
·3269-3278
·
IF 6.1
Ye-Wei Huang,Li-Tian Wang,Meng Zhang,Yan Nie,Jin-Bo Yang,Wen-Luer Meng,Xuan-Jun Wang,Jun Sheng
Increasing low-density lipoprotein receptor (LDLR) protein levels represents a key strategy for the prevention and treatment. Berberine can reportedly alleviate non-alcoholic fatty liver disease (NAFLD) by increasing the LDLR expression in an ERK1/2 signaling-dependent manner of NAFLD. Studies have shown that caffeine can inhibit fat deposition in the livers of mice; however, caffeine has not been reported to alleviate NAFLD by augmenting the LDLR expression via targeting EGFR. Here, an MTT assay, western blotting, RT-qPCR, immunohistochemistry, and surface plasmon resonance (SPR) analysis were used to investigate the role of caffeine in low-density lipoprotein cholesterol (LDL-C) clearance both in vitro and in vivo. In vitro, we found that caffeine could activate the EGFR-ERK1/2 signaling pathway in HepG2 cells, leading to increased LDLR mRNA and protein expression, and this effect could be inhibited by cetuximab. The SPR assay results have indicated that caffeine may increase the LDLR expression by directly binding to the EGFR extracellular domain and activating the EGFR-ERK1/2 signaling pathway. In vivo, caffeine markedly improved fatty liver and related blood indices in ApoE KO mice with high-fat-diet-induced NAFLD. Consistent with our in vitro results, we found that caffeine could also activate EGFR-ERK1/2 signaling and promote the LDLR expression in ApoE KO mice. In summary, caffeine can enhance the LDLR expression by directly binding to EGFR and activating the EGFR-ERK1/2 signaling pathway. EGFR signaling may represent a novel target for the prevention and treatment of NAFLD.
研究领域:
药理学
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分子生物学
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细胞生物学
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病理生理学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 24
·16211-16221
·
IF 3.9
Chunxiao Wang,Ruifu Zhao,Zhen Wang,Tingting Xu,Peng Huang
Atherosclerosis (AS), a chronic inflammatory disease, is the leading cause of death worldwide. Anti-oxidative therapy has been developed for AS therapy in light of the critical role of ROS in pathogenesis of AS, but current anti-oxidants have exhibited limited outcomes in the clinic. Herein, new ROS-eliminating liposome-like NPs (Tempol-Lips) were assembled from synthetic lipids that covalently conjugated two Tempol molecules with phosphatidylcholine by esterification reaction. The obtained Tempol-Lips can be efficiently internalized into inflammatory macrophages and attenuated inflammation via scavenging overproduced intracellular ROS. After i.v. administration, Tempol-Lips with nanoscale character accumulated in the plaques of ApoE−/− mice through passive targeting and significantly inhibited the pathogenesis of AS, compared with those treated with control drugs. The therapeutic benefits of Tempol-Lips primarily are ascribed to the reduced local and systematic oxidative stress and inflammation. Preliminary studies in vivo further demonstrated Tempol-Lips were safe and biocompatible after long-term i.v. injection. Conclusively, Tempol-Lips can be developed as a novel anti-AS nanotherapy with potential translation in the clinic.
研究领域:
心血管疾病
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纳米医学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 43
·20246-20255
·
IF 7.233
Ri Ji,Xiaoyu Li,Chun Zhou,Qiwei Tian,Chang Li,Shujun Xia,Ronghui Wang,Yun Feng,Weiwei Zhan
Macrophage recruitment has emerged as the crucial force driving the initiation and progression of atherosclerotic lesions. Therefore, the identification of macrophages in plaques is of vital importance for identifying vulnerable plaques, and noninvasive imaging methods are particularly desirable. Some studies have reported that MRI can detect plaque macrophages through targeted nanoparticles, but it is still hard for an US to detect macrophages in atherosclerotic plaque. In this study, anti-CD68 receptor-targeted Fe-doped hollow silica nanoparticles (CD68-Fe-HSNs) were fabricated as a dual-modal US/MRI contrast agent for identifying macrophages of aorta ventralis atherosclerotic plaques in ApoE–/– mice, confirmed by immunofluorescence and bio-TEM. This system possesses biodegradable characteristics even though it is an inorganic mesoporous nanosystem, indicating its potential high biocompatibility for further in vivo research. We expect that these dual-modal US/MRI nanoparticles will play a role in assessing vulnerable plaque in future research studies.
研究领域:
生物医学工程
·
分子影像学
·
纳米技术
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·
IF 6.1
Zouyan HE,Hanyue Zhu,Jianhui Liu,Erika Kwek,Ka Ying Ma,Zhen-Yu Chen
Trimethylamine-N-oxide (TMAO), originating from dietary trimethylamine-containing nutrients such as choline, has been recognized as a risk factor for atherosclerosis. Mangiferin is a bioactive xanthone initially extracted from mango (Mangifera indica). The present study aimed to investigate the effect of mangiferin on TMAO-induced atherogenesis in mice fed a high-choline diet. Female ApoE-/- mice were randomly divided into three groups and fed either a control diet, a high-choline diet with 1% free choline, or an experimental diet with 1% free choline plus 0.5% mangiferin for 15 weeks. Our results showed that a high-choline diet elevated plasma TMAO level, accelerated atherogenesis, promoted cholesterol accumulation, and reduced the generation of short-chain fatty acids (SCFAs) by gut microbes. Mangiferin alleviated inflammation, and lowered plasma total cholesterol level by facilitating the elimination of neutral and acidic sterols in feces, resulting in a 16.7-29.0% reduction in aortic atherosclerotic lesions. Notably, mangiferin could favorably remodel the composition of gut microbiota by fostering the growth of the beneficial taxa Akkermansia, Parabacteroides, and Bifidobacteriaceae, while reducing the relative abundance of the pathogenic genus Helicobacter. This modulation led to a decrease in plasma lipopolysaccharide level, enhanced production of total SCFAs by gut microbes, and reduced susceptibility to atherosclerosis. In conclusion, mangiferin exhibited its ability to alleviate TMAO-induced atherosclerosis through its anti-inflammatory, cholesterol-lowering, and gut microbial modulatory activities.
研究领域:
心血管疾病
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营养学
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微生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-19
·
IF 15.7
Zhang Lei,AL-Ammari Abdulrahman,Zhu Danxuan,Zhang Hongsong,Zhou Peng,Zhi Xu,Ding Weixiao,Li Xinmeng,Yu Qingqing,Gai Yuwen,Ma Xiaoling,Chen Chuntao,Zuo Chao,Zhang Jiaan,Zhu Wanying,Sun Dongping
Vaccines offer prophylactic treatments against atherosclerosis by eliciting effector T cell and antibody responses, which require effective delivery of antigen and adjuvant to activate dendritic cells (DC). Here we show that individual conjugation of antigen p210 and adjuvant CpG oligodeoxynucleotides onto superparamagnetic iron oxide nanoparticles formulates a nanovaccine cocktail that activates DCs for antigen cross-presentation and induction of co-stimulatory signals, cytokines and CD8 + effector/effector memory T cell responses. This nanovaccine modulates the DCs in the draining lymph nodes, activates both CD4 + and CD8 + T cells, elicits memory responses, and induces both anti-p210 IgM and IgG antibodies to suppress atherosclerosis. Lastly, three intradermal vaccinations of this nanovaccine mitigate the atherosclerosis development in the ApoE −/− mice. Our nanovaccine design and preclinical data thus presents a potential candidate for prophylactic treatment for atherosclerosis.
研究领域:
免疫学
·
心血管疾病
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纳米医学
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疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Xiaolin Ma,Xuan Zhao,Yulong Yang,Jinjin Yan,Xiaoyan Shi,Hongfei Wu,Yarong Liu,Min Dai
Atherosclerosis is a chronic inflammatory disease characterized by lipid streaks, which are produced by aggregates of lipid-rich foam cells. Foam cells intensify atherosclerosis by secreting a range of inflammatory mediators. Neutrophil extracellular traps produced by activated neutrophils, which are abundantly present in lipid-accumulating plaques. However, the relationship between neutrophil extracellular traps and foam cells inflammation is still unclear. Paeonol is well known for its anti-inflammatory effects in atherosclerosis. Nevertheless, the exact pharmacological mechanisms by which paeonol affects atherosclerosis are not fully understood which require further investigation. The purpose of this study is to investigate the effects of paeonol on the neutrophil extracellular traps' formation and foam cell inflammation caused by neutrophil extracellular traps, and to explore the potential mechanisms. A high-fat diet was administered to ApoE −/− mice for a period of 12 weeks to induce an atherosclerosis model. Our findings demonstrated that paeonol notably suppressed the advancement of atherosclerosis in ApoE −/− mice, curtailed the formation of neutrophil extracellular traps, and lowered inflammatory factor levels within the plaque. In vitro studies have shown that neutrophil extracellular traps could enhance the inflammation in foam cells. CitH3 played a role in the cellular communication between neutrophil extracellular traps and foam cells. Concurrently, NLRP3 acted as a key receptor in the inflammation mediated by this interaction. Paeonol is capable of regulating NE, thereby affecting the formation of neutrophil extracellular traps. Most notably, the foam cell inflammation caused by neutrophil extracellular traps was significantly mitigated by the inclusion of paeonol. Our findings suggested that paeonol inhibited foam cell inflammation which induced by neutrophil extracellular traps through the CitH3/NLRP3/caspase-1 signaling pathway, shedding new lights on its anti-atherosclerotic pharmacological mechanism.
研究领域:
心血管疾病
·
炎症
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药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）