Journal of Inflammation Research
·
2025
·
IF 4.1
Han-Xu Zhu,Jin-Ling Ren,Wen-Juan Cao,Rui Wang,Lei-Lei Chen,Qing Gao,Ye-Bo Zhou
Background Atherosclerotic cardiovascular diseases (CVD) are commonly found in obesity. Endothelial inflammation accompanied by oxidative stress is a crucial risk factor and a key initiating step for the pathogenesis of atherosclerosis (AS). In the present study, the role and mechanism of intermedin (IMD), a potent active peptide, in endothelial damage in AS in obese apolipoprotein E-deficient (apoE−/−) mice were investigated.Methods and Results In vivo, IMD1-53 was infused via Alzet mini-osmotic pump in apoE−/− mice with high-fat diet (HFD) for 4 weeks. In vitro, palmitic acid (PA) and oxidized low density lipoprotein (Ox-LDL) were used to stimulate human umbilical vein endothelial cells (HUVECs) for exploring the potential mechanism of IMD1-53 action on endothelial damage. We found that IMD1-53 application remarkably improved plasma lipid profiles, hepatic lipid accumulation and its cholesterol levels, and vascular lipid accumulation and lesion sizes. Moreover, IMD1-53 markedly increased eNOS expression and decreased the levels of vascular inflammatory factors and ROS. In vitro, the combination of PA and Ox-LDL caused more severe inflammatory and oxidative damages and lower expression of eNOS, which were significantly inhibited by IMD1-53. IMD1-53 notably induced AMPK phosphorylation, and the inhibition of AMPK activation markedly reversed the anti-inflammatory and antioxidant effects of IMD1-53 on PA and Ox-LDL-treated HUVECs.Conclusion IMD1-53 improves AS partially by reducing endothelial inflammatory and oxidative damage via AMPK signaling pathway and decreasing vascular lipid accumulation involving the improvement of lipid profiles in blood and in liver in a state of obesity.
研究领域:
心血管疾病
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2025
·
IF 5.4
Shenji Yang,Xiaojun Huang,Xiajialong Li,Jing Feng,Peng Chen,Zhikang Cao,Luyao He,Chaojun Li,Zhipeng Li,Ming-Yong Xie
Cardiovascular diseases are leading causes of death globally, often manifesting after years of atherosclerosis (AS) progression. In this study, we investigated the atheroprotective effects of three different sources of glucomannan, Dendrobium officinale polysaccharide, Konjac glucomannan, and Aloe vera polysaccharide (AVP) using an in vitro ox-LDL induced foam cell model and an in vivo high-fat high-cholesterol diet-fed ApoE-/- mouse model. Both settings indicate that AVP exerts the most significant atheroprotective effects. It inhibits lipid absorption and enhances the regulation of lipid homeostasis by Liver X Receptor, thereby suppressing the formation of foam cells. It can also alleviate ox-LDL-induced oxidative stress and apoptosis in RAW 264.7 cells. Animal experiments show that AVP can prevent the formation of atherosclerotic plaques and coronary artery fibrosis, while also reducing circulating IL-1β levels. Furthermore, liver transcriptomic analysis shows that AVP inhibits inflammation, and promotes bile acid excretion and transport by upregulating Farnesoid X Receptor. Additionally, metagenomic analysis indicates that AVP can significantly reverse the microbial alterations associated with AS. Specific gut microbes, such as Prevotella, may partially mediate the effects of AVP through the gut-liver axis. This is the first study to report the atheroprotective effects of AVP, demonstrating that it alleviates atherosclerosis by restoring lipid metabolism homeostasis and modulating the gut microbiome.
研究领域:
生物学
·
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ATHEROSCLEROSIS
·
2024
·
IF 4.9
Wang-Xin Liu,Yi-Fan Hu,Guang-Jie Tai,Yan-Ping Li,Jia-Peng Li,Shu Qiu,Rui-Fang Zheng,Xiao-Xue Li,Ming Xu
Background and aims Atherosclerotic cardiovascular disease complicated by diabetes mellitus (DM) is the leading cause of death in diabetic patients, and it is strongly associated with macrophages and inflammasomes. It has been found that activation of NLRP3 inflammasome is closely associated with phosphatidylinositol 4-phosphate (PI4P) on the trans-Golgi. However, how PI4P and NLRP3 regulate macrophage function and its role in diabetic atherosclerotic plaques is unclear. Methods The expression of Pi4p and Nlrp3-inflammasome-related proteins in atherosclerosis in apolipoprotein E-deficient ( Apoe -/- ) and Apoe -/- DM mice were investigated. Then, Pi4p levels were affected by shRNA-Pi4kb or cDNA-Sac1 plasmid to investigate the effects of changes in Pi4p-related metabolic enzymes on macrophage function. Finally, the genetically modified macrophages were injected into diabetic Apoe -/- mice to explore their effects on the pathology of atherosclerosis. Results DM promoted plaque progression in atherosclerotic mice and increased expression of Pi4p and Nlrp3 on plaques. In addition, impaired macrophage function induced by high glucose was reversed by transfected shRNA-Pi4kb or cDNA-Sac1 plasmid. Furthermore, it was demonstrated that decreased levels of Pi4p reduced plaque area in diabetic Apoe -/- mice. Conclusions Taken together, our data suggested that Pi4p/Nlrp3 in macrophages plays an important role in the exacerbation of atherosclerosis in diabetic mice. Pi4p-related metabolizing enzymes (PI4KB and SAC1) may be the potential therapeutic strategy for diabetic atherosclerosis, and macrophage therapy is also a potential treatment.
研究领域:
心血管疾病
·
糖尿病
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
·
2020
·Vol. 75
·期 4
·321
·
IF 2.598
Cao Qian,Du Hongjiao,Fu Xi,Duan Na,Liu Changhe,Li Xiaodong
Artemisinin is an endoperoxide sesquiterpene lactone from Artemisia annua L with multiple beneficial effects, including anti-inflammation, antioxidant, and vascular protection. Recent studies have found that inflammation along with autophagy deficiency in macrophages is the possible reason for foam cell accumulation in the intima, which leads to atherosclerotic plaque formation. The primary aims of this study were to explore the inhibiting effect of artemisinin on atherosclerosis in high-fat diet–fed ApoE −/− mice and investigate the probable mechanism. Artemisinin (50 and 100 mg/kg, intragastric administration) treatment effectively inhibited foamy macrophage transformation and decreased atherosclerotic plaque formation in atherosclerotic mice. Moreover, artemisinin promoted AMP-activated protein kinase (AMPK) activation, inhibited mammalian target of rapamycin (mTOR) and uncoordinated-51-like kinase 1 (ULK1) phosphorylation, and increased LC-3II accumulation and P62 degradation, thereby enhancing macrophage autophagy . Besides, the inhibiting effect of artemisinin on mTOR and ULK1 phosphorylation could be abrogated by AMPK knockdown, suggesting AMPK was the essential target of artemisinin on promoting macrophage autophagy . Our study indicated that artemisinin alleviated atherosclerotic lesions by accelerating macrophage autophagy through the AMPK/mTOR/ULK1 pathway.
研究领域:
药理学
·
心血管疾病
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ALZHEIMERS DISEASE
·
2019
·Vol. 67
·期 4
·1353-1365
·
IF 3.517
Aluganti Narasimhulu Chandrakala,Mitra Connie,Bhardwaj Deepshikha,Burge Kathryn Young,Parthasarathy Sampath
Background:Alzheimer’s disease (AD) is a neurodegenerative disorder associated with aging. Cardiovascular risk factors like hypertension and atherosclerosis increase the risk for AD. Polymorphic alleles of apolipoprotein E (ApoE) are one of the main genetic determinants of AD. Objective:Mice, double-knockout (DKO) for ApoE (major cholesterol carrier in brain) and PON1 (paroxonase1, reduces oxidative stress), showed severe age-dependent atherosclerosis of the arteries carrying blood to the brain even on normal diet. This prompted us to investigate the possibility of an AD pathology resulting from the deficiency of ApoE and the induction of oxidative stress. Methods:Atherosclerotic lesions were quantified by ImageJ. The brain hippocampus of young and old ApoE-PON1 DKO mice and control mice were harvested. RT-PCR analysis was performed for mRNA levels of AD specific markers. Blood levels of S100 calcium-binding protein B (S100B) protein were measured by ELISA. H&E as well as immunostaining was performed to detect amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) in brain tissues. Evans blue dye was used to evaluate the vascular permeability and blood-brain barrier (BBB) dysfunction. Results:Results showed that the older DKO mice had severe carotid atherosclerosis, increased mRNA levels of AD markers in brain tissue, and elevated levels of serum S100B protein. Immunological staining confirmed the characteristics of AD. Ex-vivo imaging showed higher levels of Evans blue dye in the ApoE-PON1 DKO mice brain tissues, pointing toward impaired vasculature. Conclusion:Aged ApoE-PON1 DKO mice displaying AD specific markers along with Aβ plaques, NFTs, and disrupted BBB suggests the animals are suffering from AD.
研究领域:
神经退行性疾病
·
分子生物学
·
病理学
·
心血管研究
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION
·
2025
·
IF 3.3
Rui Liu,Songxue Wang,Zhifu Liu,Qian Cheng,Qiuyuan Liang,Jian Du,Huali Wang,Ye Zhang,Hao Wang
Selenium-rich yeast (SeY) is a dietary supplement known to confer multiple health benefits, but its effects on HFD-fed ApoE−/− mice were previously unclear. In this study, it was shown that the intervention of SeY could decrease the body weight (7.69%), as well as the levels of both TC and TG for livers (43.36 and 14.50%) and serum (25.34 and 28.67%). Conversely, the HDL-C levels were increased high to 190%, as well as the antioxidant capacity, reflected in the increased levels of the CAT, SOD, and GSH-Px in both the liver (16.93, 22.06, and 17.59%) and the serum (40.67, 113.76, and 19.83%). SeY could further regulate mRNA levels related to lipid synthesis and transport. Moreover, the anti-hyperlipidemic effects of SeY were manifested in enriching SCFAs-producing bacteria, and the cognitive impairment caused by HFD was also alleviated. Overall, all of the results indicated the effect of SeY in regulating abnormal lipid metabolism and developing functional dietary supplements.
研究领域:
营养学
·
分子生物学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2024
·
IF 4.8
Zhihao Xu,Zhixiang Lv,Huijiao Yang,Jiashuo Zhang,Zijie Sun,Dawei He,Ruijiang Liu
A label-free electrochemical DNA detection strategy based on self-assembled α-Fe 2 O 3 /Fe 3 O 4 nanosheets with PNA-DNA hybridization process was developed for ultrasensitive detection of APOE ε4 gene, one of the most robust genetic risks for Alzheimer’s Disease (AD). In this work, magnetic α-Fe 2 O 3 /Fe 3 O 4 heterogeneous nanosheets were prepared by hydrothermal-calcined reduction method and loaded with Au nanoparticles (AuNPs) on their surfaces. The magnetic α-Fe 2 O 3 /Fe 3 O 4 @Au nanocomposites significantly enhanced the electrochemical response as a signal amplification matrix and were able to bind to the magnetic glassy carbon electrode (MGCE) surface by magnetic self-assembly. Moreover, owing to the high specificity and stable binding capacity of PNA with respect to the target DNA, the biosensor not only enabled accurate (the limit of detection was estimated to be 0.147 pM) and rapid detection of the APOE ε4 gene, but also exhibited excellent specificity, stability and regeneration capability. Additional, the satisfactory recoveries were also obtained in real samples of human serum, ranging from 92.83 % to 106.22 % with relative standard deviation (RSD) between 0.25 % and 1.85 %. The results possessed important reference value for exploring the application of DNA biosensor technology in the diagnosis of APOE gene mutation.
研究领域:
生物传感器技术
·
医学诊断
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Cardiovascular Disorders
·
2024
·Vol. 24
·期 1
·1-13
·
IF 2
Liu Hai-Hua,Wei Wei,Wu Fei-Fei,Cao Lu,Yang Bing-Jie,Fu Jia-Ning,Li Jing-Xia,Liang Xin-Yue,Dong Hao-Yu,Heng Yan-Yan,Zhang Peng-Fei
Background Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. Methods In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. Results Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. Conclusions These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
研究领域:
心血管药理学
·
炎症
·
血管生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
He Rong-rong,Ma Chuan-rui,He Xin,Dong Yan-xi,Li Hui,Chu Zi-xuan,Yang Xi-he,Wang Jia-qi,Wang Ting,Wang Feng-qing,Du Fei-fei,Rao Ying,Yu Wen-xuan,Gao Xiu-mei,Fan Guan-wei,Cheng Chen,Li Chuan
Translational pharmacological research on traditional medicines lays the foundation for precisely understanding how the medicines function in the body to deliver therapeutic benefits. Borneolum syntheticum (Bingpian) is commonly used in Chinese herbal medicines for coronary heart disease, but its specific cardiovascular impact remains poorly understood. Isoborneol, a constituent of Bingpian, has been found to reduce lipid accumulation in macrophages in vitro, but its oral bioavailability is limited. This investigation aimed to evaluate anti-atherosclerotic effects of Bingpian, based on understanding its first-pass metabolism. Human subjects orally received an herbal medicine containing Bingpian and their plasma samples were analyzed to identify the major circulating compounds of Bingpian, with the metabolism that was also characterized in vitro and in mice. The identified compounds were evaluated for their ability to inhibit macrophage foam-cell formation induced by oxidized low-density lipoprotein. Furthermore, the anti-atherosclerotic effect of repeatedly dosed Bingpian was assessed in ApoE −/− mice fed a high-fat diet. In human subjects, the major circulating compounds of Bingpian were metabolites, rather than their precursor constituents borneol and isoborneol. These constituents were efficiently absorbed in the intestinal tract but underwent significant first-pass metabolism, involving UGT2B7-mediated glucuronidation into borneol-2- O -glucuronide and isoborneol-2- O -glucuronide, respectively, and CYP2A6/2B6/3A-mediated oxidation both into camphor. Despite their poor membrane permeability, hepatic efflux of borneol-2- O -glucuronide and isoborneol-2- O -glucuronide into the systemic circulation was enhanced by MRP3/4. The circulating metabolites, particularly their combinations, markedly inhibited macrophage foam-cell formation induced by oxidized low-density lipoprotein in vitro. Sub-chronic administration of Bingpian (30 mg·kg −1 ·d − 1 , i.g.) for 12 weeks significantly decreased atherosclerotic lesion size and enhanced plaque stability in ApoE −/− mice. Systemic exposure to Bingpian metabolites in mice closely resembles that in humans, suggesting that the pharmacodynamic effects of Bingpian in mice are likely applicable to humans. Overall, the cardiovascular benefits of Bingpian involve reducing atherosclerosis by inhibiting foam-cell formation through its metabolites. This investigation supports that oral Bingpian could be a druggable agent for reducing atherosclerosis.
研究领域:
药理学
·
心血管疾病
·
传统中药
·
代谢
·
转化研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Cuiyuan Jin,You Weng,Yi Zhang,Zhiwei Bao,Guiling Yang,Zhengwei Fu,Yuanxiang Jin
Propamocarb is a systemic carbamate fungicide used to fight diseases. The effect of propamocarb on the formation of atherosclerosis was evaluated in wild-type (WT) and ApoE knockout (ApoE −/− ) mice. C57BL/6 J WT mice were fed control diet or high-fat diet (HFD) with 20 mg/L propamocarb in drinking water for 24 weeks. Propamocarb significantly increased the serum levels of triglyceride, cholesterol and low-density lipoprotein cholesterol while decreasing high-density lipoprotein cholesterol. Simultaneously, propamocarb facilitated lipid accumulation in the liver and increased the expression of cholesterol synthesis and transport genes in the liver and ileum. Lipid accumulation was observed in the aortic roots of the propamocarb-treated mice fed HFD, and similar results were also observed with whole aorta staining. In addition, propamocarb exposure significantly increased the mRNA levels of IL-1β , TNF-α , ICAM-1 , and VCAM-1 in the aorta and the serum IL-1β, IL-6, and TNF-α levels in HFD groups treated with propamocarb. In ApoE −/− mice, the results were consistent with those obtained in WT mice after exposure to 20 mg/L propamocarb for 10 weeks. Meanwhile, propamocarb significantly increased the levels of CD36, NF-κB, VCAM-1 and ICAM-1 proteins in the aortas of ApoE −/− mice. Propamocarb further disrupted cholesterol metabolism and enhanced atherosclerosis and inflammatory responses much more substantially, indicating that propamocarb has the potential to accelerate the formation of atherosclerosis. An analysis of gut microbiota revealed that propamocarb altered the composition of gut microbiota in both WT and ApoE −/− mice. Interestingly, propamocarb increased the abundance of Peptostreptococcaceae, Ruminococcaceae, and Clostridiales_VadinBB60_group , which are related to atherosclerosis at the family level. The abundance of Paeniclostridium, Allobaculum, and Clostridioides , which are closely related to atherosclerosis, was also increased by propamocarb exposure. Our findings indicate that propamocarb exposure may promote atherosclerosis by disrupting lipid metabolism, increasing the inflammatory response, and altering the structure of gut microbiota.
研究领域:
药理学
·
心血管疾病
·
免疫学
·
微生物学
·
代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antibiotics-Basel
·
2024
·Vol. 13
·期 3
·278
·
IF 4.3
Chun Wang,Yun-Yao Ren,Li-Mei Han,Peng-Cheng Yi,Wei-Xiao Wang,Cai-Yun Zhang,Xiu-Zhen Chen,Ming-Zhe Chi,Apeng Wang,Wei Chen,Chun-Mei Hu
Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, includingMycobacterium smegmatis. However, our study reveals a previously unknown resistance mechanism developed byM. smegmatisagainst COG1410 involving ClpC. Upon subjectingM. smegmatisto serial passages in the presence of sub-MIC COG1410, resistance emerged. The comparative genomic analysis identified a point mutation in ClpC (S437P), situated within its middle domain, which led to high resistance to COG1410 without compromising bacterial fitness. Complementation of ClpC in mutant restored bacterial sensitivity. In-depth analyses, including transcriptomic profiling and in vitro assays, uncovered that COG1410 interferes with ClpC at both transcriptional and functional levels. COG1410 not only stimulated the ATPase activity of ClpC but also enhanced the proteolytic activity of Clp protease. SPR analysis confirmed that COG1410 directly binds with ClpC. Surprisingly, the identified S437P mutation did not impact their binding affinity. This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance.
研究领域:
微生物学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2026
·
IF 5.5
Weihua Zhang,Ning Yang,Boyu Wen,Lihui Qin,Jianhui Jiang,Yifang Wang,Mei Huang,Ruichen Wang,Lili Wu,Fuan Zhang,Guozhen Cui,Tonghua Liu
BackgroundAtherosclerosis remains a leading cause of cardiovascular morbidity and mortality worldwide. Although camellia oil exhibits promising anti-atherosclerotic properties, its direct consumption is often limited by its strong flavor and greasy texture.ObjectiveThis study aimed to develop a camellia oil-based beverage with a milky appearance, reduced greasiness, and enhanced palatability. In addition, the anti-atherosclerotic effects of the beverage were examined in ApoE−/− mice.MethodsA camellia oil-based oil-in-water emulsion was optimized and characterized for stability, particle size, and zeta potential. Its anti-atherosclerotic effects were evaluated in high-fat diet-fed ApoE−/− mice after 8 weeks of treatment using aortic Oil Red O staining, serum lipid assays, and UHPLC-Q-TOF/MS-based metabolomics.Results and conclusionIn ApoE−/− mice, the beverage treatment significantly reduced aortic plaque burden, achieving an efficacy comparable to that of unprocessed camellia oil, thereby demonstrating that emulsification preserved its bioactivity. Additionally, the beverage significantly lowered serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol (p < 0.05). Untargeted metabolomic profiling further indicated that its protective effects were associated with the modulation of metabolic pathways involved in lipid regulation. Taken together, these findings highlight the camellia oil-based beverage as a promising dietary strategy for mitigating atherosclerosis and improving lipid homeostasis.
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）