BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Youming Shi,Wenjiao Gu,Yujie Wei,Shuangyi Li,Shining Zhang,Ying jiang,Chuanjian Chen,Ting Liu,Limei Shuai,Xiaochun Zhou,Futian Tang
Purpose Atherosclerosis (AS) and atherosclerotic calcification (AC) are closely related to the cardiovascular diseases, largely due to its induction of vasomotor dysfunction. We previously reported that Calpain-1 inhibitor attenuated AS and AC. The present study was designed to investigate the effects and potential mechanisms of Calpain-1 knockout (Calpain-1 KO) in Apolipoprotein E KO (ApoE KO) mice on AS, AC, aortic vasomotor function as well as the liver dysfunction. Methods We hybridized ApoE KO mice with Calpain-1 KO mice to obtain ApoE /Calpain-1 double KO (A×C DKO) mice. The formation of AS and AC was evaluated and liver function was determined. Aortic vasomotor function was assessed. Contents of TNF-α, IL-6, IL-18, IL-1β and NO and the activity of AST, ALT, ALP and eNOS in serum were quantified. The mRNA expression of CD68, SR-A, CD36, PPAR-γ, LXR-α, ABCA1, BMP-2, OPN, ALP and Runx2 in aorta and/or liver were measured. Results The results showed that in comparison to C57 mice, ApoE KO mice demonstrated the significant increases in the areas of AS and AC, the increases in the mRNA expression of CD68 in the aorta, the increases in the AST, ALT and ALP activity in serum. ApoE KO mice also showed the dysfunction of the aortic contraction induced by phenylephrine and of the relaxation induced by acetylcholine. However, compared with ApoE KO mice, A×C DKO mice exhibited the significant attenuation of AS and AC and the downregulation of mRNA expression of CD68 in aorta. A×C DKO mice revealed the reduction of AST, ALT and ALP activity in serum, the improvements in aortic contraction and relaxation as well as the increases in eNOS activity and NO content in serum. A×C DKO mice also showed the decreases in the contents of TNF-α, IL-6, IL-18 and IL-1β in serum. The mRNA expression of CD68 in aorta, SR-A and CD36 in both aorta and liver of A×C DKO mice was downregulated, while that of PPAR-γ, LXR-α, and ABCA1 was upregulated in comparison of ApoE KO mice. In addition, the mRNA expression of BMP-2, OPN, ALP and Runx2 in aorta of A×C DKO mice was downregulated in comparison of ApoE KO mice. Conclusion The results suggested that deficiency of Calpain-1 attenuated the formation of AS and AC and improved vasomotor and liver dysfunction in ApoE KO mice through anti-inflammation, and modulation of the mRNA expression of genes related to AS and AC.
研究领域:
心血管疾病研究
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 10
·5103-5114
·
IF 3.289
Zongyuan Wu,Zumeng Xia,Bangfu Wu,Fang Wei,Xin Lv,Ya Xie,Shuling Xu,Jiqu Xu,Hong Chen,Fenghong Huang
Atherosclerosis is a chronic disease associated with oxidative stress and inflammatory activation and is the main underlying trigger for cardiovascular disease. There are many cardiovascular health products in the market; in order to evaluate the effect of these products, in this paper, a novel lipid profiling platform was established using the shot-gun mass spectrum method for the analysis of free fatty acid and phospholipids, and the high performance liquid chromatography coupled with mass spectroscopy method for the analysis of lipid mediators and triacylglycerol, respectively, in serum from male apolipoprotein E-knock out mice after different diet interventions. Changes in the four lipids above, and pathways and regulation of lipid metabolism in mice from different groups were further investigated. The result showed that all cardiovascular health products showed some certain potential to alleviate atherogenesis and ameliorate inflammation; among them, lemon apple cider vinegar drink and seal oil could significantly decrease triacylglycerol in mouse serum. The establishment of this lipidome profiling platform helps to better understand the metabolism regulation and intervention mechanism of different cardiovascular health products in chronic diseases, such as atherogenesis. This platform could be applied to other cardiovascular health products and provide reliable lipid profiling data for their potential effect.
研究领域:
生物化学
·
代谢组学
·
心血管病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Gangyuan Lin,Qidi He,Jiadong Cai,Xiujuan Yang,Yong Wang
Single-nucleotide polymorphisms (SNPs) can be relevant to disease susceptibility, disease pathogenesis, and efficacy of specific drugs. Monitoring SNPs plays a significant role in disease susceptibility and individual response to treatment, wherein optimal care can be provided to individuals based on their unique genetic and disease profiles. In this work, we have formulated a rapid and sensitive fluorescent biosensing platform based on a target-activated triple-helix molecular switch (THMS)-conformation-change-induced invader assay strategy for the detection of single nucleotide polymorphisms in the apolipoprotein E ( APOE ). The mutant DNA (MtDNA) of APOE gene hybridized with the THMS to form the three-dimensional invader structure over the SNP site. Subsequently, the specific structure would be recognized and cleaved by FEN1, leading to the recovery of FAM quenched by BHQ 1. Based on the high binding affinity of THMS to the target, our strategy could detect the MtDNA of AOPE gene without amplification at 0.27 nM. Furthermore, we achieved genotyping based on the difference in fluorescence signals and successfully applied this strategy to detect MtDNA of APOE gene in clinical samples, showing the great potential for monitoring various SNPs for biological research and disease diagnosis.
研究领域:
分子生物学
·
医学诊断
·
遗传学
✓ 已验证
产品关联
DOI
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
TISSUE & CELL
·
2023
·
IF 2.6
Ying Wang,Yongjun Li,Dongxia Liu
Background This study aimed to investigate role of erythropoietin in atherosclerosis and explore whether underlying mechanism is associated with PI3K/AKT/mTOR pathway. Methods High-fat-diet-induced atherosclerosis model was established in apolipoprotein E knockout mice (C57BL/6 genetic background). Mice were randomly divided into the control group and the EPO group. Hematoxylin-eosin was performed for the determination of atherosclerotic lesions. The expression levels of related proteins were detected by western blot analysis . Results Erythropoietin significantly enhanced the incidence of hemorrhage in atherosclerotic plaques compared with the control group. The proteins’ expression signaling pathways (including PI3K , AKT, and mTOR) and angiogenesis-related proteins (VEGF, COX-2, and HIF-1α) were proved to be up-regulated by erythropoietin. Additionally, erythropoietin significantly enhanced the incidence of hemorrhage in the atherosclerotic plaques compared with the control group. The vitro experiments were conducted in macrophages at 21% O 2 or 1% O 2 . The data showed that expression of p -PI3K, p -AKT, p -mTOR, VEGF, COX-2, and HIF-1α related proteins increased in 1% O 2 group than 21% O 2 group. Moreover, compared with control group, protein expression including p -PI3K, p -AKT, p -mTOR, VEGF, COX-2, and HIF-1α was markedly increased in EPO group, decreased in inhibitors group, and similar results were observed in EPO+ inhibitors group. Conclusion The present study demonstrated that erythropoietin might promote angiogenesis in atherosclerotic vulnerable by activating PI3K/AKT/mTOR signaling pathway in atherosclerotic, providing a novel therapeutic target for atherosclerotic targeted therapy.
研究领域:
心血管疾病
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2023
·
IF 4.8
Zeyu Xing,Mingyang Du,Yanhua Zhen,Jie Chen,Dongdong Li,Ruyin Liu,Jiahe Zheng
Atherosclerosis (AS), a metabolic disorder , is usually caused by chronic inflammation. LETM1 Domain-Containing Protein 1 (LETMD1) is a mitochondrial outer membrane protein required for mitochondrial structure. This study aims to evaluate the functional role of LETMD1 in endothelial pathogenesis of AS. Oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) and high-fat diet apolipoprotein E -deficient (ApoE −/− ) mice were used to establish in vitro and in vivo models, respectively. Recombinant adenovirus vectors were constructed to investigate the role of LETMD1 in AS. mRNA sequencing was used to explore the effect of LETMD1 overexpression on gene expression in ox-LDL-induced HUVECs. A dual-luciferase reporting assay and chromatin immunoprecipitation (ChIP)-PCR were further conducted to verify the relationship between KLF4 and LETMD1. Results showed that LETMD1 was highly expressed in the aortas of atherosclerotic animals. LETMD1 overexpression reduced the expression of inflammatory factors, pyroptosis , ROS production, and NF-κB activation in ox-LDL-induced HUVECs, whereas LETMD1 knockdown had the opposite impact. LETMD1 overexpression was involved in regulating gene expression in ox-LDL-induced HUVECs. Overexpression of LETMD1 in mice reduced serum lipid levels as well as atherosclerotic lesions in the aortic roots. Furthermore, LETMD1 overexpression suppressed inflammatory reactions, cell pyroptosis, nuclear p65 protein level, cell apoptosis, and ROS generation in the aortas of AS mice. KLF4 (Krüppel-like factor 4) was found to be the transcriptional regulator of LETMD1. In conclusion, LETMD1, a target of KLF4, hinders endothelial inflammation and pyroptosis, which is a mechanism inhibiting the development of atherosclerosis.
研究领域:
心血管疾病
·
分子生物学
·
细胞生物学
·
炎症
·
转录调控
✓ 已验证
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
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Heng Ye,Gang Wang,Xuchao Wang,Lin Wang,Wei Ni,Linjian Chen,Yifan Zhu,Longshan Zhao,Zhili Xiong,Yan Wang,Cuilian Dai,Binbin Liu
Ethnopharmacological relevance Dyslipidemia is the leading risk factor of atherosclerosis (AS). Adipose tissue macrophages (ATMs) can regulate postprandial cholesterol levels via uptake and hydrolyzation of lipids and regulation of macrophage cholesterol efflux (MCE). San-wei-tan-xiang (SWTX) capsule , a Traditional Chinese medicine , exerts clinical benefits in patients with atherosclerotic cardiovascular diseases . Aim of the study This work is aimed to evaluate the chemical ingredients and mechanisms of SWTX in anti-AS. Materials and methods The chemical ingredients of SWTX identified by liquid chromatography coupled with tandem mass spectrometry were used for network pharmacological analysis. The atheroprotective function of SWTX was evaluated in ApoE −/− mice fed a cholesterol-enriched diet. Results The chemical ingredients identified in SWTX were predicated to be important for lipid metabolism and AS. Animals studies suggested that SWTX effectively attenuated the atherosclerotic plaque growth, elevated postprandial HDL cholesterol levels, elevated the proportion of Tim4 and CD36-expressed ATMs, and upregulated the uptake of lipid and lysosomal activity in ATMs. SWTX-induced elevation of postprandial HDL cholesterol levels was dependent on increased lysosomal activity, since chloroquine , an inhibitor of lysosomal function, blocked the effect of SWTX. Lastly, some predicated bioactive compounds in SWTX can elevate lysosomal activity in vitro . Conclusion SWTX could attenuate atherosclerotic plaque formation by elevating lysosomal activity and enhancing MCE in ATMs.
研究领域:
药理学
·
心血管疾病
·
传统中药
·
代谢
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Bingwei Yang,Zhishuai Ye,Xiangyu Zhu,Rongchong Huang,Erqun Song,Yang Song
Further investigations are required to prove that polychlorinated biphenyls (PCBs) exposure is a cardiovascular disease risk factor. Unlike previous studies that attributed the atherogenic effect of PCBs to aryl hydrocarbon receptor activation, we illustrated a new mechanism involved in the redox reactivity of PCBs. We discover the redox reactivity of quinone moiety is the primary factor for PCB29-pQ-induced proinflammatory response, which highly depends on the status of caveolin 1 (CAV1) phosphorylation. PCB29-pQ-mediated CAV1 phosphorylation disrupts endothelial nitric oxide synthase, toll-like receptor 4, and reduces interleukin-1 receptor-associated kinase 1 binding with CAV1. Phosphorylated proteomics analysis indicated that PCB29-pQ treatment significantly enriched phosphorylated peptides in protein binding functions, inflammation, and apoptosis signaling. Meanwhile, apolipoprotein E knockout (ApoE -/- ) mice exposed to PCB29-pQ had increased atherosclerotic plaques compared to the vehicle group, while this effect was significantly reduced in ApoE -/- /CAV1 -/- double knockout mice . Thus, we hypothesis CAV1 is a platform for proinflammatory cascades induced by PCB29-pQ on atherosclerotic processes. Together, these findings confirm that the redox activity of PCB metabolite plays a role in the etiology of atherosclerosis.
研究领域:
心血管疾病
·
毒理学
·
分子生物学
·
药理学
✓ 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
危险品化学品经营许可证（带存储）