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Objective To investigate effects of oxidized low density lipoprotein/β2 glycoprotein- I/anti- β2 glycoprotein-I antibody (oxLDL/β2GPI/aβ2GPI) complex on the proliferation, migration and angiogenesis of vascular endothelial cells and its mechanism. Methods Human umbilical vein endothelial cells (HUVEC) were cultured to logarithmic growth phase and grouped into the control group (normal culture), the oxLDL group (50 mg/L oxLDL), the oxLDL/ β2GPI/aβ2GPI group (50 mg/L oxLDL/100 mg/L β2GPI/100 mg/L aβ2GPI) and the VEGF group (100 µg/L VEGF). The gene expressions of VEGF, vascular endothelial cadherin (VE-cadherin), matrix metalloproteinase (MMP)-2 and MMP9 were detected by real-time quantitative fluorescent PCR (qPCR). Cell counting kit-8 (CCK-8) method was employed to detect cell proliferation. Cell migration and invasion were determined by scratch healing test and Transwell assay. Matrigel tube formation assay was used to observe the angiogenesis of HUVEC. The relative protein expression of TLR4, MyD88 and NF-κB were examined by Western blot assay. Results Compared with the control group, the proliferation activity of cells at 48 h of treatment was increased in the oxLDL/β2GPI/aβ2GPI group (P＜0.05). Moreover, compared with the control group, cell migration and angiogenesis were increased in the oxLDL/β2GP I/aβ2GP I group, and the mRNA levels of VEGF, VE-cadherin, MMP-2 and MMP-9 were elevated (P＜0.05). Compared with the control group, levels of TLR4 and MyD88 were elevated in the oxLDL/β2GPI/aβ2GPI complex group (P＜0.05), as well as levels of p-NF-κB p65/NF-κB p65 (P＜0.05). Conclusion oxLDL/β2GP I/aβ2GP I complex may promote the proliferation, migration and tube formation of vascular endothelial cells by regulating TLR4/MyD88/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is a risk factor for atherosclerosis and includes impaired endothelium-dependent vasodilatation. We have shown previously that low density lipoprotein (LDL) can be oxidized by iron in the lysosomes of macrophages. Macrophage lysis in atherosclerotic lesions might expose endothelial cells to this oxidized LDL and adversely affect their function. LDL was oxidized by ferrous sulfate (5 µM) for 24 h at pH 4.5 at 37 °C. Aortas from male Wistar rats were cut into rings and subjected to wire myography for isometric tension recording. The rings were incubated with or without oxidized LDL (50 µg protein/ml) for one hour, constricted with 100 nM phenylephrine and relaxation to acetylcholine (1 nM − 3 µM) was measured. There was about 50% less relaxation in the presence of this oxidized LDL. Endothelial-independent vasodilatation induced by sodium nitroprusside was less affected by oxidized LDL. Oxidized LDL increased the formation of reactive oxygen species by the aortic rings and by cultured human aortic and dermal microvascular endothelial cells, which might have inactivated nitric oxide. Acetylcholine increased the activatory phosphorylation of eNOS (ser-1177), but oxidized LDL had little effect on this activation in cultured human aortic endothelial cells. These findings raise the possibility that LDL oxidized in lysosomes and released from lysed macrophages might decrease vasodilatation in atherosclerotic arteries. [ABSTRACT FROM AUTHOR]

Objective to explore the risk assessment potential of oxLDL in patients with T2DM combined with PTB. Methods A prospective study was conducted, which included 60 cases of simple hyperlipidemia, 100 cases of PTB, 100 cases of T2DM, and 100 cases of T2DM combined with PTB. These patients visited the outpatient department of our center from June 2022 to June 2023. The PTB group, T2DM group, and T2DM combined with PTB group were further divided into subgroups based on normal blood lipids (40 cases) and hyperlipidemia (60 cases), totaling 360 cases in the case group. Additionally, a control group consisting of 60 healthy individuals was included. The age range for inclusion in the study was between 35 to70 years old. Venous blood samples were collected from each group to detect HbA1c, INS, FSG, CHOL, TG, HDL, LDL, ApoA I and Apo B. OxLDL levels were measured using the ELISA method. Differences in levels between groups were compared. Multivariate logistic regression analysis was applied to assess the association between oxLDL levels and PTB as well as T2DM combined with PTB. Results There were no statistically significant differences in BMI, blood sugar, blood lipids, and insulin resistance between the T2DM hyperlipidemia subgroup and the T2DM combined with PTB hyperlipidemia subgroup. The oxLDL level in the T2DM hypertipidemia subgroup was more than double that of the control group, while the oxLDL level in the subgroup with normal blood lipids was significantly higher than that of the control group. Moreover, both the T2DM combined with PTB hyperlipidemia subgroup and simple hyperlipidemia group exhibited significantly elevated levels of oxLDL compared to the control group: however, there were no statistically significant differences when compared to the PTB hyperlipidemia subgroup. Correlation analysis revealed a significant positive linear correlation between TG and LDL with oxLDL in both the T2DM hyperlipidemia subgroup and the T2DM combined with PTB hyperlipidemia subgroup (R = 0.352, P < 0.05) . Additionally, CHOL and LDL levels in the PTB hyperlipidemia subgroup also showed a significant positive correlation with oxLDL (R = 0.441, P < 0.05) . Multivariate logistic regression analysis indicated that having oxLDL levels more than double that of the control group was an independent risk factor for both PTB and T2DM combined with PTB (P < 0.05) . Conclusion The significantly elevated levels of oxLDL may serve as a potential risk factor for the comorbidity of T2DM and PTB. It is recommended to consider oxLDL levels exceeding twice those of the control group as a clinically meaningful pathological threshold for further assessment. [ABSTRACT FROM AUTHOR]

Background Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes. Methods We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin. Results Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin. Conclusion We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

Abstract Background The oxidative modification of low density lipoprotein (LDL) is closely associated with an increased risk for coronary artery disease (CAD) in diabetic patients. The purpose of this study is to investigate the relation between serum vitamin E and selenium, paraoxonase-1 (PON1) activity, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and oxidative stress index (OSI) values with the susceptibility of LDL to oxidative modification and the possibility of CAD in diabetic patients. Method This study was designed as a case control survey of 82 diabetes patients divided into two groups including T2DM alone (as group I) and both T2DM and CAD (as group II). Fasting blood samples were taken to the assay of fasting blood glucose (FBG), HbA1c, total cholesterol (TC), TAC, TOS, MDA, OSI, vitamin E, selenium, oxidized low density lipoprotein (Ox-LDL), and activity of PON1. Results Ox-LDL, MDA, TOS, and OSI values in groups II were significantly higher compared with group I (all with P value = 0.000). TAC, vitamin E, selenium, and PON1 activity values were significantly lower in group II compared with groups I (P value = 0.000; P value = 0.000; P value = 0.007; P value = 0.003, respectively). There were significant relationships between the amounts of TAC, TOS, OSI, and vitamin E with the amounts of PON1 activity and Ox-LDL (p

Objective To explore the mechanism of lipid metabolism disorder promoting the progress of lung cancer based on the oxidized low density lipoprotein (ox⁃LDL)/ human lectin⁃like oxidized low density lipoprotein receptor 1 (LOX 1) signaling pathway. Methods Eighty one identified lung adenocarcinoma tissues with paired adjacent non⁃cancerous tissues (at least 5 cm away from the tumor) were collected from our hospital, and the expression of LOX⁃1 was detected by immunohistochemistry. LOX⁃1 was overexpressed in lung adenocarcinoma cell lines (A549 and H1299 cells). Cell invasion ability was measured by Transwell. Cells were treated with different concentrations of oxLDL, and cellular LOX⁃1 expression was investigated. Results LOX⁃1 staining in the tumor was significantly stronger than that in the non⁃cancerous tissue samples (99.4 vs. 16.2 for median H score, P < 0.001). High LOX⁃1 expression was significantly correlated with low survival (P < 0.001). As compared with the patients without lymph node metastasis, those with lymph node metastasis had higher LOX⁃1 level (83.2 vs. 121.1 for median H score, P < 0.01). Overexpression of LOX⁃1 in lung cancer cells significantly promoted the number of invasive and metastatic cells (P < 0.01). In addition, LOX⁃1 was an essential functional target for oxLDL⁃induced metastasis of lung cancer cells. Itatinib inhibited the metastasis of LOX⁃1 overexpressed A549 in vitro. Conclusions With an increase in oxLDL level, the expression of LOX⁃1 increases. Up⁃regulation of LOX⁃1 promotes metastasis of lung cancer, and its mechanism may be related to activation of the JAK1/STAT6 signaling pathway. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) regulate the function of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) progression. We aimed to explore the role of circUSP9X in oxidized low-density lipoprotein (ox-LDL)- induced VSMCs. Cell proliferation was assessed using cell counting kit-8 and EDU assays. Cell migration was evaluated using Transwell and wound healing assays. The interaction between circUSP9X or STIM1 and miR-599 was analyzed using dual-luciferase reporter and RNA pull-down assays. Their levels were examined using quantitative real-time PCR. CircUSP9X and STIM1 expression was increased, whereas miR-599 expression was reduced in the serum of patients with AS and ox-LDL-stimulated VSMCs. Overexpression of circUSP9X facilitated the proliferation and migration of VSMCs induced by ox-LDL. CircUSP9X sponged miR-599, which targeted STIM1. MiR-599 reversed the effects induced by circUSP9X, and STIM1 reversed the effects induced by miR-599. Taken together, CircUSP9X promoted proliferation and migration in ox-LDL-treated VSMCs via the miR-599/STIM1 axis, providing a theoretical basis for the role of circUSP9X/miR-599/STIM1 axis in AS. [ABSTRACT FROM AUTHOR]

Objective Foam cell formation was an important part of the occurrence and development of atherosclerosis.To explore the role of perilipin2（PLIN2） in foam cell lipophagy, and to provide more ideas for the prevention and treatment of atherosclerosis-related diseases.Methods The foam cell model induced by oxidized low density lipoprotein（ox-LDL） was constructed, and the expression of PLIN2 gene in the cells was silenced.The cells were divided into five groups: the control group, the empty plasmid group, the ox-LDL treatment group, the siPLIN2 group, the ox-LDL+siPLIN2 group.The oil red O staining was used to observe the lipid accumulation of intracellular, and the Western blot was used to observe the expression of PLIN2 and lipophagy-related proteins LC3 and p62.Results During the formation of foam cells induced by ox-LDL,the expression of LC3 increased with the increase of lipid, while p62 decreased first and then increased.The expression of LC3 was down-regulated in PLIN2-silenced RAW264.7 macrophages.In PLIN2-silenced foam cells, the expression of p62 protein was significantly increased and lipophagy was weakened.Conclusion In ox-LDL-induced foam cells, knockdown of PLIN2 can down-regulate the expression of p62 and attenuate intracellular lipophagy. [ABSTRACT FROM AUTHOR]

Aim To explore the role of circular RNA spindle and kinetochore-associated protein 3 (circ-SKA3) in regulating Toll-like receptor 4 (TLR4) axis in atherosclerosis (As) through miR-1303. Methods Carotid artery plaque, diseased vascular tissue, normal tissue adjacent to plaque and venous blood were collected from 30 patients with As treated by carotid endarterectomy from April 2019 to April 2022. Another 30 normal venous blood samples were collected. Microarray analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect the expression and localization of circ-SKA3 in plaque tissue of As patients, control samples, plasma exosome, human umbilical vein endothelial cell (HUVEC) and aorta of As model mice. The relationship among circ-SKA3, miR-1303 and TLR4 was verified by bioinformatics, double luciferase reporter gene detection and RNA immunoprecipitation. The proliferation, migration and angiogenesis of HUVEC were detected by CCK-8, scratch, Transwell and angiogenesis experiments. TLR4 axis-related protein expression was detected by Western blotting. Pathological changes of aorta in As model mice was observed by Oil red O staining, HE staining and Masson staining. TLR4 expression in aorta of As model mice was detected by immunohistochemistry and immunofluorescence. Results The expression levels of circ-SKA3 and TLR4 in plaque tissue, plasma exosome, oxidized low density lipoprotein (ox-LDL) treated HUVEC and circ-SKA3, TLR4 in aortic of As model mice were up-regulated (P<0. 05), while the expression level of miR-1303 was down-regulated (P<0. 05). Functional analysis showed that circ-SKA3 promoted HUVEC damage in vitro and As progress in vivo. Mechanism analysis showed that circ-SKA3 could promote TLR4 expression by adsorbing miR-1303 by sponge. Inhibition of circ-SKA3/miR-1303/TLR4 axis can inhibit the formation of As lesions. Conclusions circ-SKA3 is overexpressed in carotid plaque, plasma exosome, ox-LDL-treated HUVEC and As model mouse aorta in As patients. circ-SKA3/miR-1303/TLR4 axis can promote the development of As model in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Background: The oxidative modification of low density lipoprotein (LDL) is closely associated with an increased risk for coronary artery disease (CAD) in diabetic patients. The purpose of this study is to investigate the relation between serum vitamin E and selenium, paraoxonase-1 (PON1) activity, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and oxidative stress index (OSI) values with the susceptibility of LDL to oxidative modification and the possibility of CAD in diabetic patients. Method: This study was designed as a case control survey of 82 diabetes patients divided into two groups including T2DM alone (as group I) and both T2DM and CAD (as group II). Fasting blood samples were taken to the assay of fasting blood glucose (FBG), HbA1c, total cholesterol (TC), TAC, TOS, MDA, OSI, vitamin E, selenium, oxidized low density lipoprotein (Ox-LDL), and activity of PON1. Results: Ox-LDL, MDA, TOS, and OSI values in groups II were significantly higher compared with group I (all with P value = 0.000). TAC, vitamin E, selenium, and PON1 activity values were significantly lower in group II compared with groups I (P value = 0.000; P value = 0.000; P value = 0.007; P value = 0.003, respectively). There were significant relationships between the amounts of TAC, TOS, OSI, and vitamin E with the amounts of PON1 activity and Ox-LDL (p < 0.05). But Ox-LDL and PON1 activity correlated weakly with together (p = 0.094). Conclusion: Results of this study support the belief that oxidative stress might be an important etiologic factor which makes some diabetics more susceptible to CAD. Increased oxidative stress may be a potential therapeutic target in the prevention and management of CAD in diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: In this study, pasteurized Akkermansia muciniphila (PAKK) was examined for its protective effect on oxidized low-density lipoprotein (ox-LDL)-induced injury in human aortic endothelial cells (HAEC). Methods: MTT method was used to evaluate the effect of PAKK on HAEC activity and determine the appropriate dose. A model of ox-LDL-induced cell injury was established, and the protective effect of PAKK on HAEC cell injury was evaluated by measuring lactate dehydrogenase and reactive oxygen species. By measuring the activities of antioxidant enzymes and the expression of genes and proteins related to the Nrf2 antioxidant pathway, the possible mechanisms by which PAKK ameliorated HAEC oxidative damage was discussed. Results: PAKK at the doses of 105 and 106 CFU/mL did not affect the viability of HAEC, but significantly reduced the release rate of lactate dehydrogenase induced by ox-LDL. The reactive oxygen species level was decreased, while the activity of superoxide dismutase, catalase and the total antioxidant capacity of cells were significantly increased. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutathione S-transferase (GST) and NADPH quinone oxidoreductase-1 (NQO1) were significantly up-regulated. Nrf2, HO-1 and NQO1 protein expression were also significantly enhanced. Conclusion: These findings indicated that PAKK could alleviate the injury of HAEC caused by ox-LDL, and its protective effect was partly mediated through enhanced expression of antioxidant related enzymes by regulating Nrf2 signaling pathway. This study would provide theoretical basis for development of Akkermansia muciniphila-based probiotic or postbiotic for prevention of atherosclerosis.

Aim To explore the effects of rapamycin liposomes (RL) on the migration of human aortic vascular smooth muscle cells (HA-VSMC) induced by oxidized low density lipoprotein (ox-LDL) and its mechanism related to S100 calcium binding protein A4 (S100A4). Methods Vascular smooth muscle cells were transfected with lentivirus knockdown S100A4 gene, and then added puromycin to screen stable strain of S100A4 gene knockdown. Vascular smooth muscle cells were treated with 50 mg/L ox-LDL, and different doses of RL (3, 6 and 12 mg/L) were added to observe the effect on cell migration before and after treatment. Cell migration was detected by cell scratch method and Transwell, and the expression of S100A4, phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), typeⅠcollagen protein (COLⅠ), and vimentin were detected by Western blot. Results After 48 h treatment with ox-LDL, compared with the blank control group, the expression of S100A4, p-PI3K, p-Akt, p-mTOR, COLⅠ and vimentin was significantly increased (P <0. 05), and the speed of cell migration was significantly accelerated (P<0. 05). Compared with ox-LDL group, different doses of RL significantly inhibited the expression of S100A4, p-PI3K, p-Akt, p-mTOR, COLⅠ and vimentin and significantly inhibited cell migration after 48 h treatment (P<0. 05), of which 6 mg/L and 12 mg/L of RL had more significant inhibitory effects (P < 0. 05). After S100A4 gene knockdown, the cell migration rate was significantly reduced (P < 0. 05). Conclusion RL can significantly inhibit the migration of HA-VSMC induced by ox-LDL, which may be related to the down-regulation of S100A4, p-PI3K, p-Akt, p-mTOR, COLⅠ and vimentin expression by RL. [ABSTRACT FROM AUTHOR]

Efferocytosis, responsible for apoptotic cell clearance, is an essential factor against atherosclerosis. It is reported that efferocytosis is severely impaired in fibroatheroma, especially in vulnerable thin cap fibroatheroma. However, there is a shortage of studies on efferocytosis defects in cell and animal models. Here, the impacts of oxidized low density lipoprotein (ox‐LDL) and glut 1 inhibitor (STF31) on efferocytosis of macrophages are studied, and an evaluation system is constructed. Through regulating the cell ratios and stimulus, three types of atherosclerotic spheroids are fabricated, and a necrotic core emerges with surrounding apoptotic cells. Rat models present a similar phenomenon in that substantial apoptotic cells are uncleared in time in vulnerable plaque, and the model period is shortened to 7 weeks. Mechanism studies reveal that ox‐LDL, through mRNA and miRNA modulation, downregulates efferocytosis receptor (PPARγ/LXRα/MerTK), internalization molecule (SLC29a1), and upregulates the competitive receptor CD300a that inhibits efferocytosis receptor‐ligand binding process. The foam cell differentiation has also confirmed that CD36 and Lp‐PLA2 levels are significantly elevated, and macrophages present an interesting transition into prothrombic phenotype. Collectively, the atherosclerotic models featured by efferocytosis defect provide a comprehensive platform to evaluate the efficacy of medicine and biomaterials for atherosclerosis treatment. [ABSTRACT FROM AUTHOR]

Aim To explore the clinical value of transcutaneous oxygen pressure (TcPO2) combined with serum oxidized low density lipoprotein (ox-LDL) in predicting restenosis after interventional therapy for lower arteriosclerosis obliterans (LASO). Methods 113 patients with LASO underwent interventional therapy in Yueyang Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2020 to June 2021 were enrolled, and classified into non-stenosis group (n =79) and restenosis group (n =34) according to the occurrence of restenosis 1 year after interventional treatment. Serum ox-LDL levels were detected by ELISA and corresponding assay kits, and TcPO2 was measured by laser Doppler flowmeter. Then comparison was conducted on general data, TcPO2 and ox-LDL. Multivariate Logistic regression model was used to screen the influencing factors of resteno-sis after intervention therapy for LASO. Spearman test was used for correlation analysis, ROC curve was used to evaluate the efficacy of TcPO2 and ox-LDL in predicting restenosis in LASO patients after intervention therapy. Results There was no significant difference between the two groups in age, body mass index (BMI), sex, alcohol consumption, history of cerebrovascular disease and coronary heart disease, number of diseased vessels, fasting blood glucose, and homocysteine (P>0. 05). Compared with the non-stenosis group, smoking, irregular drug use, the number of implanted stents, ox-LDL, and the level of blood uric acid in the restenosis group were significantly higher (P<0. 05), and TcPO2 was significantly lower (P<0. 05). Logistic regression model analysis showed that smoking, irregular drug use after LASO intervention, large number of implanted stents, decreased TcPO2, ox-LDL, and increased blood uric acid were the risk factors for restenosis after LASO intervention (P<0. 05). Spearman test showed that ox-LDL was positively correlated with restenosis after LASO intervention (r =0. 513, P<0. 001), and TcPO2 was negatively correlated with it (r =-0. 524, P<0. 001). The ROC curve showed that the predictive efficacy of TcPO2 +ox-LDL in predicting restenosis after LASO interventional therapy (AUC = 0. 802) was higher than that of each indicator alone. The predictive sensitivity and specificity were 67. 60% and 94. 90% respectively, and the critical point was 37. 23 mmHg and 5. 31 mmol/L. Conclusion TcPO2 is decreased and ox-LDL is increased in patients with restenosis after interventional therapy for LASO, both indicators have certain predictive value for restenosis, and combined detection of the two can reflect restenosis condition more completely. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the most frequent cause of death globally. Oxidized low-density lipoprotein (ox-LDL) has an essential role in the formation of atherosclerotic plaques and foamy macrophages. Ox-LDL increases the uptake of cholesterol by macrophages and is the major cause of blood flow disruption. Ox-LDL is produced during oxidative stress and treatment with antioxidants could inhibit the production and function of ox-LDL. Curcumin is a potent antioxidant and has a strong track record in the treatment of numerous diseases. Recent studies indicate that Curcumin exerts a lipid-lowering effect, and can modulate the formation of atherosclerotic plaque. The current review focuses upon the role of Curcumin in oxidation of LDL and foam cell formation in atherosclerotic lesions.

Abstract Background Familial hypercholesterolemia (FH) is a metabolic disease in which patients are prone to develop premature atherosclerosis (AS). Sorbin and SH3 Domain Containing 2 (SORBS2) is known to play a role in coronary heart disease (CHD). However, the mechanism underlying SORBS2 involvement in the development of hypercholesterolemia remains unknown. Here, we investigated the effects of SORBS2 on inflammation and foam cell formation and its underlying mechanisms. Methods Using Bioinformatics analysis, we established that SORBS2 is upregulated in patients with FH. Circulating concentrations of SORBS2 were measured using ELISA kit (n = 30). The association between circulating SORBS2 levels and inflammatory factors or lipid indexes were conducted using Spearman correlation analysis. We further conducted in vitro experiments that the expression of SORBS2 were analyzed, and SORBS2 siRNA were transfected into oxidized LDL (OxLDL)-induced macrophages, followed by western blot and immunofluorescence. Results Circulating SORBS2 levels were positively associated with inflammatory factors and lipid indexes. We also observed that high in vitro expression of SORBS2 in OxLDL-induced macrophages. After SORBS2 silencing, Nod like receptor family pyrin domain-containing 3 protein(NLRP3)-Caspase1 activation and NF-κB activation were attenuated, and secretion of pro-inflammatory cytokines (IL-1β and IL-18) was decreased. Moreover, SORBS2 silencing blocked reactive oxygen species (ROS) production and lipid accumulation, and promoted cholesterol efflux through ABCG1-PPARγ pathway. Conclusions SORBS2 regulates lipid-induced inflammation and foam cell formation, and is a potential therapeutic target for hypercholesterolemia.

Background/objectives: Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The p -coumaric acid ( p- CA) contained in vegetables may have various physiological activities. The inhibitory effect of p -CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of p -CA on foam cells by co-treatment with oxidized low-density lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis in vitro and studied the regulation of its underlying mechanisms., Materials/methods: THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of p -CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA., Results: Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, p -CA treatment inhibited lipid accumulation. p -CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, p -CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. p -CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6., Conclusion: p -CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis., Competing Interests: Conflict of Interest: The authors declared no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

The lymphatic vasculature of the liver is vital for liver function as itmaintains fluid and protein homeostasis and is important for immune cell transport to the lymph node. Chronic liver disease is associated with increased expression of inflammatory mediators including oxidized low-density lipoprotein (oxLDL). Intrahepatic levels of oxLDL are elevated in nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C infection (HCV), alcohol-associated liver disease (ALD), and cholestatic liver diseases. To determine if liver lymphatic function is impaired in chronic liver diseases, in which increased oxLDL has been documented, we measured liver lymphatic function in murine models of NAFLD, ALD and primary sclerosing cholangitis (PSC). We found that Mdr2-/- (PSC), Lieber-DeCarli ethanol fed (ALD) and high fat and high cholesterol diet fed (NAFLD) mice all had a significant impairment in the ability to traffic FITC labeled dextran from the liver parenchyma to the liver draining lymph nodes. Utilizing an in vitro permeability assay, we found that oxLDL decreased the permeability of lymphatic endothelial cells (LEC)s, but not liver sinusoidal endothelial cells (LSEC)s. Here we demonstrate that LECs and LSECs differentially regulate SRC-family kinases, MAPK kinase and VE-Cadherin in response to oxLDL. Furthermore, Vascular Endothelial Growth Factor (VEGF)C or D (VEGFR-3 ligands) appear to regulate VE-Cadherin expression as well as decrease cellular permeability of LECs in vitro and in vivo after oxLDL treatment. These findings suggest that oxLDL acts to impede protein transport through the lymphatics through tightening of the cell-cell junctions. Importantly, engagement of VEGFR-3 by its ligands prevents VE-Cadherin upregulation and improves lymphatic permeability. These studies provide a potential therapeutic target to restore liver lymphatic function and improve liver function. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to analyze the relationship between expression levels of chemerin, oxidized low density lipoprotein (ox‐LDL), matrix metalloproteinase 9 (MMP‐9) and pregnancy associated plasma protein A (PAPP‐A) in ischemic cerebrovascular disease (ICVD) patients and the relationship between the mentioned indicators and the degree of neurological impairment. Methods: From January 2020 to February 2021, a total of 328 cases of ICVD patients were admitted to our hospital, and 240 cases of healthy people (control group) were prospectively recruited into this study. The 328 patients were divided into 2 ischemic subtypes, with 233 cases as acute cerebral infarction (ACI) and 95 cases as transient ischemic attack (TIA). Laboratory tests were compared among the groups. Spearman rank correlation was used to analyze the correlation between chemerin, ox‐LDL, MMP‐9, PAPP‐A levels and neurological deficit. Unconditional logisitic regression was used to analyze the risk factors for neurological deficits. Results: The high density lipoprotein cholesterol (HDL‐C), fasting plasma glucose (FPG), chemerin, ox‐LDL, MMP‐9, and PPAP‐A levels in the ACI group were significantly higher than those in the TIA group and control group (p < 0.05, respectively), while the levels of the mentioned indicators in the TIA group were significantly higher than those in control group (p < 0.05, respectively). The levels of the given indicators decreased successively in the severe, moderate, and mild neurological deficits population and control group, with statistical difference. Spearman rank correlation analysis showed that chemerin, ox‐LDL, MMP‐9, and PPAP‐A levels were positively correlated with the degree of neurological deficit in ICVD patients. Unconditional logistic regression analysis showed that chemerin, ox‐LDL, MMP‐9, and PPAP‐A were the independent risk factors for neurological deficit in patients with ICVD. Conclusion: LDL‐C, FPG, chemerin, ox‐LDL, MMP‐9, and PPAP‐A were highly expressed in ACI and neurological deficit patients. Chemerin, ox‐LDL, MMP‐9, and PPAP‐A may be the independent risk factors for neurological deficit in patients with ICVD. [ABSTRACT FROM AUTHOR]

Objective: To investigate markers of carotid atherosclerosis and oxidized low density lipoprotein (OxLDL) levels in patients with Familial Mediterranean Fever (FMF) who have no risk factors for cardiovascular disease. Method: It was included 44 patients (25 F/19 M; mean age: 33.5±7.5) with FMF in attack free period and gender and age matched 44 healthy subjects (25 F/19 M; mean age: 33.4±7.0). The patients with clinical coronary artery disease, chronic renal disease, diabetes mellitus, hypertension, history of myocardial infarction, angina pectoris, cerebrovascular disease, dyslipidemia, metabolic syndrome, active infection, those in postmenopausal period, and those using anti-lipid drugs were excluded. Carotid artery intima-media thickness (C-IMT) was measured and investigated atherosclerotic plaques in the carotids by using doppler ultrasound. Serum lipid and OxLDL levels were also assessed. Data were analyzed with the SPSS program and p<0.05 were accepted as significant. Result: Mean disease duration of the FMF patients was 20±9 years. The mean C-IMT did not differ between the patient and control groups (0.52±0.10 mm, 0.53±0.06 mm, respectively, p=0.709). None of the patients or controls had atherosclerotic plaques. Total and LDL cholesterol levels were significantly lower in the patient group compared to the controls (total cholesterol: 157.07±34.18, 181.05±36.79, respectively, p=0.002; LDL cholesterol: 100.48±30.13, 126.25±34.05, respectively, p=0.001). However, we found that OxLDL levels were significantly higher in FMF patients compared to control group (337.48±438.56 ng/dl, 156.19±383.24 ng/dl, p=0.044). No correlation was found between C-IMT and OxLDL levels in both patients (p=0.324) and controls (p=0.246). Conclusion: Our study provides further evidence for no increased atherosclerosis in FMF. As previously shown, FMF patients have lower cholesterol levels compared to healthy controls. On the other hand, increased OxLDL levels could be associated with increased subclinical inflammation. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia (FH) is a metabolic disease in which patients are prone to develop premature atherosclerosis (AS). Sorbin and SH3 Domain Containing 2 (SORBS2) is known to play a role in coronary heart disease (CHD). However, the mechanism underlying SORBS2 involvement in the development of hypercholesterolemia remains unknown. Here, we investigated the effects of SORBS2 on inflammation and foam cell formation and its underlying mechanisms.Methods: Using Bioinformatics analysis, we established that SORBS2 is upregulated in patients with FH. Circulating concentrations of SORBS2 were measured using ELISA kit (n = 30). The association between circulating SORBS2 levels and inflammatory factors or lipid indexes were conducted using Spearman correlation analysis. We further conducted in vitro experiments that the expression of SORBS2 were analyzed, and SORBS2 siRNA were transfected into oxidized LDL (OxLDL)-induced macrophages, followed by western blot and immunofluorescence.Results: Circulating SORBS2 levels were positively associated with inflammatory factors and lipid indexes. We also observed that high in vitro expression of SORBS2 in OxLDL-induced macrophages. After SORBS2 silencing, Nod like receptor family pyrin domain-containing 3 protein(NLRP3)-Caspase1 activation and NF-κB activation were attenuated, and secretion of pro-inflammatory cytokines (IL-1β and IL-18) was decreased. Moreover, SORBS2 silencing blocked reactive oxygen species (ROS) production and lipid accumulation, and promoted cholesterol efflux through ABCG1-PPARγ pathway.Conclusions: SORBS2 regulates lipid-induced inflammation and foam cell formation, and is a potential therapeutic target for hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and mechanism of CXC chemokine ligand 12 (CXCL12) on oxidized low density lipoprotein (ox-LDL)-induced foaming and apoptosis of macrophages. Methods RAW264.7 was incubated with 60 mg/L of ox-LDL to induce foaming of macrophages, which was recorded as ox-LDL group, and to compare with the control without ox-LDL; si-con and si-CXCL12 were transfected to RAW264.7 cells and thenincubated with ox-LDL at 60 mg/L as ox-LDL+si-con group and ox-LDL+si-CXCL12 group, respectively. Oil Red O staining was used to detect cellular foaming; Western blot was used to detect ABCA-1, SRB-1, cleaved caspase-3, cleaved caspase-9, CXCL12, p38 mitogen-activated protein kinase (p38MAPK), and phosphorylated p38MAPK (p-p38MAPK) protein expression; flow cytometry is used to detect apoptosis; CXCL12 mRNA expression was measured by real-time fluorescence quantitative PCR(RT-qPCR). Results The size of ox-LDL-treated macrophages increased, the shape became round, and a large number of red lipid droplets were found in the cytoplasm; the expression of ABCA-1 and SRB-1 and cleaved caspase-3 as well as cleaved caspase-9 were all significantly increased; the apoptosis rate and the expression of CXCL12 and p-p38MAPK were significantly increased(P＜0.05). Silencing CXCL12, no red-stained lipid droplets were found in most cells, only a few cells had partial lipid droplets, the expressions of ABCA-1 and SRB-1 were significantly reduced, and the expression of cleaved caspase-3 and cleaved caspase-9, apoptosis rate and the expression of p-p38MAPK significantly reduced(P＜0.05). Conclusions Silencing CXCL12 inhibits ox-LDL-induced foaming and apoptosis of mouse macrophage cell line RAW264.7, which may be related to the p38MAPK signaling pathway.

Abstract Objective The study aimed to analyze the relationship between expression levels of chemerin, oxidized low density lipoprotein (ox‐LDL), matrix metalloproteinase 9 (MMP‐9) and pregnancy associated plasma protein A (PAPP‐A) in ischemic cerebrovascular disease (ICVD) patients and the relationship between the mentioned indicators and the degree of neurological impairment. Methods From January 2020 to February 2021, a total of 328 cases of ICVD patients were admitted to our hospital, and 240 cases of healthy people (control group) were prospectively recruited into this study. The 328 patients were divided into 2 ischemic subtypes, with 233 cases as acute cerebral infarction (ACI) and 95 cases as transient ischemic attack (TIA). Laboratory tests were compared among the groups. Spearman rank correlation was used to analyze the correlation between chemerin, ox‐LDL, MMP‐9, PAPP‐A levels and neurological deficit. Unconditional logisitic regression was used to analyze the risk factors for neurological deficits. Results The high density lipoprotein cholesterol (HDL‐C), fasting plasma glucose (FPG), chemerin, ox‐LDL, MMP‐9, and PPAP‐A levels in the ACI group were significantly higher than those in the TIA group and control group (p < 0.05, respectively), while the levels of the mentioned indicators in the TIA group were significantly higher than those in control group (p < 0.05, respectively). The levels of the given indicators decreased successively in the severe, moderate, and mild neurological deficits population and control group, with statistical difference. Spearman rank correlation analysis showed that chemerin, ox‐LDL, MMP‐9, and PPAP‐A levels were positively correlated with the degree of neurological deficit in ICVD patients. Unconditional logistic regression analysis showed that chemerin, ox‐LDL, MMP‐9, and PPAP‐A were the independent risk factors for neurological deficit in patients with ICVD. Conclusion LDL‐C, FPG, chemerin, ox‐LDL, MMP‐9, and PPAP‐A were highly expressed in ACI and neurological deficit patients. Chemerin, ox‐LDL, MMP‐9, and PPAP‐A may be the independent risk factors for neurological deficit in patients with ICVD.

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Oxidized LDL (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(−)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(−) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(−) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(−) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues identified in apoB. The amount of oxPC adducts of apoB was higher in the LDL(−) than in the L1 fraction, as determined using Western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(−) fraction with an anti-oxPC mAb. The majority of PC species were not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.

Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in oxidized LDL (Ox-LDL)-induced macrophage foam cell formation and inflammation is unknown and therefore was studied. In recombinant mouse granulocyte-macrophage colony-stimulating factor-differentiated murine bone marrow-derived macrophages, early (1–6 h) Ox-LDL treatment induced PKM2 tyrosine 105 phosphorylation and promotes its nuclear localization. PKM2 regulates aerobic glycolysis and inflammation because PKM2 shRNA or Shikonin abrogated Ox-LDL-induced hypoxia-inducible factor-1α target genes lactate dehydrogenase, glucose transporter member 1, interleukin 1β (IL-1β) mRNA expression, lactate, and secretory IL-1β production. PKM2 inhibition significantly increased Ox-LDL-induced ABCA1 and ABCG1 protein expression and NBD-cholesterol efflux to apoA1 and HDL. PKM2 shRNA significantly inhibited Ox-LDL-induced CD36, FASN protein expression, DiI-Ox-LDL binding and uptake, and cellular total cholesterol, free cholesterol, and cholesteryl ester content. Therefore, PKM2 regulates lipid uptake and efflux. DASA-58, a PKM2 activator, downregulated LXR-α, ABCA1, and ABCG1, and augmented FASN and CD36 protein expression. Peritoneal macrophages showed similar results. Ox-LDL induced PKM2- SREBP-1 interaction and FASN expression in a PKM2-dependent manner. Therefore, this study suggests a role for PKM2 in Ox-LDL-induced aerobic glycolysis, inflammation, and macrophage foam cell formation.

The accumulation of cholesterol-bearing macrophage foam cells in the initial stages of atherosclerosis serves as a characteristic feature of atherosclerotic lesions. The inhibitory effect of Siegesbeckia glabrescens , a species of flowering plant in the Asteraceae family, on foam cell formation in THP-1 macrophages has not yet been elucidated. In this study, we explored the effect of S. glabrescens ethanol extract (SGEE) and hot water extract (SGWE) on foam cell formation via co-treatment with oxidized low density lipoprotein (ox-LDL) and lipopolysaccharide (LPS), mimicking the occurrence of atherosclerosis in vitro , and studied the regulation of its underlying mechanisms. THP-1 cells differentiated by PMA (1 μM) for 48 h were subsequently treated with/without SGWE and SGEE for 48 h. THP-1 macrophages were treated with ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. Treatment with ox-LDL and LPS for 24 h enhanced the lipid accumulation in foam cells compared to in untreated cells, as determined by oil red O staining. In contrast, SGWE and SGEE treatment inhibited lipid accumulation in foam cells. Both extracts significantly upregulated ABCA1, LXRα, and PPARγ expression in ox-LDL- and LPS-treated cells ( P <0.05). Moreover, both SGWE and SGEE decreased LOX-1, CD36, and SR-A1 expression. The co-treatment of ox-LDL and LPS increased NF-κB, COX-2, and pro-inflammatory activation and expression compared with untreated cells. However, this increase suppressed NF-κB, COX-2, and pro-inflammatory expression by SGWE and SGEE. The results indicated that both extracts can partially inhibit foam cell formation and contribute to protective effects by suppressing cholesterol accumulation during the onset of atherosclerosis., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (© 2024 The Korean Society of Food Science and Nutrition.)

Atherosclerosis is the most frequent cause of death globally. Oxidized low-density lipoprotein (ox-LDL) has an essential role in the formation of atherosclerotic plaques and foamy macrophages. Ox-LDL increases the uptake of cholesterol by macrophages and is the major cause of blood flow disruption. Ox-LDL is produced during oxidative stress and treatment with antioxidants could inhibit the production and function of ox-LDL. Curcumin is a potent antioxidant and has a strong track record in the treatment of numerous diseases. Recent studies indicate that Curcumin exerts a lipid-lowering effect, and can modulate the formation of atherosclerotic plaque. The current review focuses upon the role of Curcumin in oxidation of LDL and foam cell formation in atherosclerotic lesions. [ABSTRACT FROM AUTHOR]

Oxidized low density lipoprotein (Ox-LDL) plays an important role in the pathogenesis of atherosclerosis. Recently, we identified two fluorescence-labeled heptapeptides, (FITC)KP6 and (FITC)dKP6, that bind specifically to lyso- and oxidized-phosphatidylcholine (LPC and Ox-PC), both of which are generated during LDL oxidation and are known to be major bioactive lipid components of Ox-LDL. Here, we report an in vitro method to assess oxidative status of LDL by specific binding of (FITC)KP6 and (FITC)dKP6 to LPC and ox-PC in Ox-LDL. Briefly, LDL with a candidate was oxidized by copper ions, and the reaction mixture with (FITC)KP6 or (FITC)dKP6 was subjected to non-denaturing polyacrylamide gel electrophoresis. The gels were visualized and characterized using a luminescent image analyzer. This method may provide important information about the oxidative status of LDL by measuring LPC and Ox-PC generated during LDL oxidation in conjunction with other oxidation assays such as thiobarbituric acid–reactive substances (TBARS) and the production of LDL conjugated dienes and also be useful for searching inhibitors and promoters of atherosclerosis. [ABSTRACT FROM AUTHOR]

Adaptive immunity, which plays an important role in the development of atherosclerosis, is mediated by major histocompatibility complex (MHC)-dependent antigen presentation. In atherosclerotic lesions, macrophages constitute an important class of antigen-presenting cells that activate adaptive immune responses to oxidized low-density lipoprotein (OxLDL). It has been reported that autophagy regulates adaptive immune responses by enhancing antigen presentation to MHC class II (MHC-II). In a previous study, we have demonstrated that SYK (spleen tyrosine kinase) regulates generation of reactive oxygen species (ROS) and activation of MAPK8/JNK1 in macrophages. Because ROS and MAPK8 are known to regulate autophagy, in this study we investigated the role of SYK in autophagy, MHC-II expression and adaptive immune response to OxLDL. We demonstrate that OxLDL induces autophagosome formation, MHC-II expression, and phosphorylation of SYK in macrophages. Gene knockout and pharmacological inhibitors of NOX2 and MAPK8 reduced OxLDL-induced autophagy. Using bone marrow-derived macrophages isolated from wild-type and myeloid-specific SYK knockout mice, we demonstrate that SYK regulates OxLDL-induced ROS generation, MAPK8 activation, BECN1-BCL2 dissociation, autophagosome formation and presentation of OxLDL-derived antigens to CD4(+) T cells. ldlr(-/-) syk(-/-) mice fed a high-fat diet produced lower levels of IgG to malondialdehyde (MDA)-LDL, malondialdehyde-acetaldehyde (MAA)-LDL, and OxLDL compared to ldlr(-/-) mice. These results provide new insights into the mechanisms by which SYK regulates MHC-II expression via autophagy in macrophages and may contribute to regulation of adaptive immune responses in atherosclerosis.

Intrauterine growth restriction(IUGR) affects about 9% of whole pregnancies. It is known that there is an increased risk of mortality and morbidity in infants. It is a serious disease that causes complications such as acute and chronic pulmonary diseases, necrotizing enterocolitis, intraventricular hemorrhage and retinopathy in the future. We aimed to study the role of oxidized low density lipoprotein (OxLDL), which is an significant risk factor in cardiovascular diseases, in IUGR and its relationship with thiol homeostasis. 38 women with IUGR and 38 healthy pregnant were included in this study. Serum total thiol and native thiol levels were analyzed with fully automatic autoanalysers in patients and controls. Serum OxLDL levels were also measured by ELISA method. According to the results of the study, it was found that OxLDL was significantly higher in the patient group compared to the control group (27.29±3.32 and 10.64±1.05 ng/mL, respectively, p <0.05). However, there was no significant difference between thiol parameters (p> 0.05).In addition, there was a negative correlation between oxLDL and native thiol and OxLDL and total thiol in the IUGR group. Oxidative stress is an important factor in the formation of OxLDL.OxLDL is an effective molecule in all stages of atherosclerosis. It appears that increased oxidative stress in IUGR patients increases OxLDL. Increased OxLDL in pregnancies complicated by IUGR may increase the risk of developing cardiovascular disease for both mother and fetus later in life. Therefore, developing treatment for OxLDL in IUGR patients may protect both mother and child from future dangers. [ABSTRACT FROM AUTHOR]

Accumulation of cholesterol‐laden macrophage foam cells characteristic of early stage atherosclerotic lesions. Phenethyl isothiocyanate (PEITC) is a naturally occurring isothiocyanate found in cruciferous vegetables that has reported a variety of activities including antioxidant and anti‐inflammatory properties. However, the protective effect of PEITC on foam cell formation and its precise mechanism is not yet clear. Therefore, we investigated whether PEITC suppresses foam cell formation and regulates the expression of genes related to lipid accumulation, cholesterol efflux, and inflammation in THP‐1 derived‐macrophages. We exposed THP‐1 derived‐macrophages to oxidized low‐density lipoprotein (ox‐LDL) (20 μg/mL) and lipopolysaccharide (LPS) (500 ng/ml) to mimic foam cell formation. Here, PEITC downregulated the expression of lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), cluster of differentiation 36 (CD36), scavenger receptor A1 (SR‐A1), and nuclear factor‐κB (NF‐κB), while upregulated ATP binding cassette subfamily A member 1 (ABCA1)/liver‐X‐receptor α (LXR‐α)/peroxisome proliferator‐activated receptor gamma (PPARγ) and sirtuin 1 (SIRT1) expression compared to co‐treated with ox‐LDL and LPS. Taken together, PEITC, at least in part, inhibits foam cell formation and reduces lipid accumulation in foam cells. Therefore, we suggest that PEITC may be a potential candidate for the treatment and prevention of vascular inflammation and atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerosis is considered as a systemic disease which leads to functional and structural changes in several segments of the arterial system. Morbidity and mortality are mostly caused by Peripheral arterial occlusive disease (PAOD). Vascular endothelium, which is a versatile multifunctional tissue, had synthetic and metabolic properties. Endothelial injury may be responsible, for the initiation of atherosclerosis and vascular lesions which are followed by monocyte infiltration, macrophage differentiation, and migration of smooth muscle cells. von Willebrand factor (vWF), acts as a glycoprotein synthesized mainly by endothelial cells, and is an indicator to endothelial damage. It represents the most sensitive marker of peripheral atherosclerosis. Moreover, intima-media thickness (IMT) increasing is used as a non-invasive of early arterial wall alteration marker and is one method of assessing the development of early atherosclerosis. The Peroxisome proliferator-activated receptors (PPARs) regulate both lipid and lipoprotein metabolism and glucose homeostasis so they influence cellular's proliferation, differentiation and cell apoptotic process. PPAR-alpha activity occurs by leukotriene B4, while, PPAR-gamma activator is the oxidized low-density lipoprotein (ox-LDL). PPAR activation decreases the incidence of cardiovascular disease. Leukotriene B4 (LTB4) causes vascular permeability and attraction and activation of leukocytes. So, Oxidized low-density lipoprotein (ox-LDL) plays a crucial role in the inflammatory process genesis occurring in the atherosclerotic lesion. Increased ox-LDL levels have a direct relation to the acute coronary syndromes severity. The levels of vWF, LTB4 and ox-LDL were measured to find the relationship between these parameters and the severe effects of the disease. [ABSTRACT FROM AUTHOR]

The effect and molecular mechanism of melatonin on the vascular smooth muscle cells proliferation and vascular smooth muscle cells migration induced by oxidized low density lipoprotein was explored in this paper. The first scheme: induce vascular smooth muscle cells with series of oxidized low density lipoprotein concentrations for 48 h (0 μg/mL, 10 μg/mL, 20 μg/mL, 50 μg/mL and 100 μg/mL). The second scheme: 50 μg/mL oxidized low density lipoprotein was used to induce vascular smooth muscle cells s for 0 h, 6 h, 12 h, 24 h and 48 h. The third option: first induce vascular smooth muscle cells with 50 μg/mL oxidized low density lipoprotein for 24 h, then treat vascular smooth muscle cells with series of melatonin concentrations for 48 h (1 nmol/L, 1 μmol/L, 0.1 mmol/L, 1 mmol/L). Cell Counting Kit-8 method was used to detect cell proliferation. Cells were randomly divided into blank control group, melatonin group (0.1 mmol/L melatonin treatment vascular smooth muscle cells 48 h), oxidized low density lipoprotein group (vascular smooth muscle cells were induced by 50 μg/ml oxidized low density lipoprotein for 24 h), oxidized low density lipoprotein +melatonin group (50 μg/ml of oxidized low density lipoprotein induced vascular smooth muscle cells for 24 h and then treated vascular smooth muscle cells s with 0.1 mmol/L of melatonin for 48 h). After relative treatment, cell cycle was detected by flow cytometry and cell migration was detected by scratch test. Proliferating cell nuclear antigen, alpha smooth muscle actin, cyclin A and extracellular regulatory protein kinase were detected by immunofluorescence staining and Western blot 1/2 (extracellular regulatory protein kinase 1/2) signal pathway related protein expression. Compared with the blank control group, vascular smooth muscle cells s treated with 50 μg/ml oxidized low density lipoprotein could significantly induce cell proliferation. After 24 h of induction by oxidized low density lipoprotein (50 μg/ml), the number of cells in S phase and G1 phase was decreased significantly and the number of cells in G2 phase was increased significantly. Cell migration was promoted and proliferating cell nuclear antigen, cyclin A, Cyclina, p-extracellular regulatory protein kinase 1/2 protein expression was up-regulated, down regulating the p-p21 protein level. The difference was statistically significant (p<0.01). The melatonin with series concentrations (1 nmol/L, 1 μmol/L, 0.1 mmol/L and 1 mmol/L) could inhibit the proliferation of vascular smooth muscle cells induced by oxidized low density lipoprotein to varying degrees. After vascular smooth muscle cells treatment with oxidized low density lipoprotein (50 μg/ml) for 24 h and melatonin (0.1 mmol/L) for 48 h, the cells in G1 and S phase increased significantly, the cells in G2 phase decreased significantly, the cell migration was inhibited, which were compared with oxidized low density lipoprotein oxidized low density lipoprotein group. The expression of proliferating cell nuclear antigen, cyclin A, Cyclina, p-extracellular regulatory protein kinase 1/2 protein was decreased and the expression of p-p21 protein was up-regulated, the difference was statistically significant (p<0.01). Melatonin can significantly inhibit the proliferation and migration of vascular smooth muscle cells induced by oxidized low density lipoprotein and its mechanism may be related to activating p21 and blocking extracellular regulatory protein kinase 1/2 signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Propolis, a polyphenol-rich natural product, has been used as a functional food in anti-inflammation. However, its bioactive components and mechanisms have not been fully elucidated. To discover the bioactive components and anti-inflammatory mechanism, we prepared and separated 8 subfractions from ethyl acetate extract of Chinese propolis (EACP) and investigated the mechanism in oxidized low density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) damage. Methods Eight subfractions were prepared and separated from ethyl acetate extract of Chinese propolis (EACP) with different concentrations of methanol-water solution, and analysed its chemical constituents by HPLC-DAD/Q-TOF-MS. Then 80% confluent HUVECs were stimulated with 40 μg/mL ox-LDL. Cell viability and apoptosis were evaluated by Sulforhodamine B (SRB) assay and Hoechst 33,258 staining, respectively. Levels of caspase 3, PARP, LC3B, p62, p-mTOR, p-p70S6K, p-PI3K, p-Akt, LOX-1 and p-p38 MAPK were assessed by western blotting and immunofluorescence assay, respectively. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Results Each subfraction exhibited similar protective effect although the contents of chemical constituents were different. EACP attenuated ox-LDL induced HUVECs apoptosis, depressed the ratio of LC3-II/LC3-I and enhanced the p62 level. In addition, treatment with EACP also activated the phosphorylation of PI3K/Akt/mTOR, and deactivated the level of LOX-1 and phosphorylation of p38 MAPK. The overproduction of ROS and the damage of MMP were also ameliorated after ECAP treatment. Conclusions These findings indicated that the bioactive component of propolis on anti-inflammatory activity was not determined by a single constituent, but a complex interaction including flavonoids, esters and phenolic acids. EACP attenuated ox-LDL induced HUVECs injury by inhibiting LOX-1 level and depressed ROS production against oxidative stress in ox-LDL induced HUVECs, further to activate PI3K/Akt/mTOR pathway and deactivate p38 MAPK to inhibit apoptosis and autophagy, which provide novel insights into the potential application of propolis on modulating chronic inflammation.

Coronary heart disease (CHD) is caused when cholesterol carried in blood form plaque in the covering of coronary arteries leading to atherosclerosis. The diminished nitric oxide (NO) production and inflammation are involved in the development of atherosclerosis. The pathogenesis of atherosclerosis is implicated by decreased availability of NO. Reduced NO level in the endothelium makes it vulnerable and increases the passage of leukocyte and LDL oxidation in the sub endothelial space which ultimately leads to CHD. The objective of this study is to evaluate the association of NO and ox-LDL along with hs-CRP in subjects with CHD. This cross-sectional study showed that the mean NO levels were decreased significantly in CHD group compared with that in the controls. A significant increase in Oxidized LDL and hs-CRP was observed in CHD group when compared with that of controls. Increased oxidative stress associated with diminished bioavailability of nitric oxide undergoes oxidative modification of LDL leading to low grade inflammation. [ABSTRACT FROM AUTHOR]

Purpose: High-density lipoprotein (HDL) undergoes structural and functional modification in patients with type 2 diabetes mellitus (T2DM). There are limited data on effect of rosuvastatin on HDL-associated proteins and the antiatherogenic effects of rosuvastatin. The present study intended to study the efficacy of rosuvastatin intervention on HDL-associated proteins and its other antiatherogenic effects in men with T2DM. Methods: Men with T2DM on oral antidiabetic treatment, with LDL-C levels > 75 mg/dL and willing for rosuvastatin intervention (20 mg/day orally for a period of 12 weeks), were included. Fasting glucose, lipid profile were measured using standard methods. Oxidized low-density lipoprotein (oxLDL), oxidized HDL (oxHDL), paraoxonase-1 (PON-1), tumour necrosis factor-α (TNF-α) and lecithin:cholesterol acyltransferase (LCAT) in serum were measured by ELISA; serum myeloperoxidase (MPO) by spectrophotometric method and cholesterol efflux by fluorometric assay. Carotid intima-media thickness (cIMT) measurement to assess vascular health status was done using doppler. Results: Rosuvastatin produced a significant decrease (p < 0.05) in lipids (total cholesterol, triglycerides, LDL-C); oxidative stress (oxLDL, oxHDL, MPO); inflammation (TNF-α); LCAT concentration; cIMT; significant increase in antiatherogenic HDL and cholesterol efflux (p < 0.05) and no change in apoA-I levels from baseline to 12 weeks of follow-up. A decrease in MPO activity was found to be independently associated with an increase in cholesterol efflux. Conclusions: Post intervention there is a quantitative and qualitative improvement in HDL, which helps in its reverse cholesterol transport (RCT) and antioxidant functions. Improvement in HDL functions and suppression of inflammation by rosuvastatin lead to regression in cIMT, which is beneficial in decreasing the progression of cardiovascular disease (CVD) in men with diabetes. [ABSTRACT FROM AUTHOR]

Low-density lipoprotein (LDL) and oxidized low-density lipoprotein (oxLDL) levels are thought to be related to recurrent stroke. However, the joint association of circulating LDL and oxLDL levels with the outcomes of acute minor ischemic stroke and transient ischemic attack (TIA) remains unclear. The goal of the study was to evaluate whether LDL and oxLDL have a combined effect on outcomes of acute minor stroke and TIA. In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, a subgroup of 3019 patients with baseline oxLDL and LDL levels were analyzed. Patients were divided into four groups according to different combinations of LDL (LDL < 3.37 mmol/L, LDL ≥ 3.37 mmol/L) and oxLDL levels (oxLDL <13.96 μg/dL, oxLDL ≥ 13.96 μg/dL). The primary outcome was any stroke within 90 days. The secondary outcomes included any stroke within 1 year and ischemic stroke and combined vascular events within 90 days and 1 year. The poor functional outcome included modified Rankin Scale (mRS) 3–6 at 90-day and 12-month follow-up. The association of LDL and oxLDL with the prognosis of patients was examined using multivariable Cox regression models. Among 3019 patients included in this study, the medians (interquartile range) of oxLDL and LDL were 13.96 (6.65–28.81) μg/dL and 3.1 (2.5–3.8) mmol/L, respectively. The cumulative occurrence of recurrent stroke, ischemic stroke, and combined vascular events was 9.74%, 9.54%, and 9.80% within 90 days of follow-up. Compared with those with low LDL and oxLDL levels (LDL < 3.37 mmol/L with oxLDL <13.96 μg/dL), patients with high levels of LDL and oxLDL (LDL ≥3.37 mmol/L, oxLDL ≥13.96 μg/dL) had significantly increased risk of recurrent stroke at 90 days (HR,1.57; 95% CI, 1.10–2.24) and 1 year (HR,1.49; 95% CI, 1.10–2.04). Patients in groups with LDL ≥3.37 mmol/L, oxLDL <13.96 μg/dL (HR,1.35; 95% CI, 0.94–1.93) or LDL < 3.37 mmol/L with oxLDL ≥13.96 μg/dL (HR,1.11; 95% CI, 0.77–1.59) showed no statistical difference for stroke recurrence. Similar results were found for functional outcomes. The presence of higher combined serum oxLDL and LDL levels was associated with increased risk of recurrent stroke and poor functional outcomes in minor stroke or high-risk TIA patients. Image 1 • The combination of oxLDL and LDL can predict recurrent stroke independently in patients with minor stroke or transient ischemic attack (TIA). • The combination of oxLDL and LDL can also predict poor functional outcomes. • Combined utility of oxLDL and LDL may be more useful in patients with minor stroke or TIA. [ABSTRACT FROM AUTHOR]

The functional heterogeneity of HDL is attributed to its diverse bioactive components. We evaluated whether the vasodilatory effects of HDL differed across HDL subpopulations, reflecting their distinct molecular composition. The capacity of five major HDL subfractions to counteract the inhibitory effects of oxidized LDL on acetylcholine-induced vasodilation was tested in a rabbit aortic rings model. NO production, an essential pathway in endothelium-dependent vasorelaxation, was studied in simian vacuolating virus 40-transformed murine endothelial cells (SVECs). Small dense HDL3 subfractions displayed potent vasorelaxing activity (up to +31% vs. baseline, P < 0.05); in contrast, large light HDL2 did not induce aortic-ring relaxation when compared on a total protein basis. HDL3 particles were enriched with sphingosine-1-phosphate (S1P) (up to 3-fold vs. HDL2), with the highest content in HDL3b and -3c that concomitantly revealed the strongest vasorelaxing properties. NO generation was enhanced by HDL3c in SVECs (1.5-fold, P < 0.01), a phenomenon that was blocked by the S1P receptor antagonist, VPC 23019. S1P-enriched reconstituted HDL (rHDL) was a 1.8-fold (P < 0.01) more potent vasorelaxant than control rHDL in aortic rings. Small dense HDL3 particles displayed potent protective effects against oxidative stress-associated endothelium dysfunction, potentially reflecting their elevated content of S1P that might facilitate interaction with S1P receptors and ensuing NO generation.

Aim. To assess biochemical and genetic markers associated with the level of oxidized low density lipoproteides (oxLDL).Material and methods. Patients with various cardiovascular risk according to the SCORE scale were included in this study. Biochemical parameters were measured in blood serum with automatic analyzer Architect C8000 (Abbott, USA). OxLDL level was measured with the hard-phase immune-enzyme assay Oxidized LDL ELIsA (Mercodia, sweden). Genotyping was performed via the Cardio-MetaboChip microarrays (Illumina, USA). Seventeen single-nucleotide polymorphisms (SNP) of the APOB gene were included into analysis: rs676210, rs1042034, rs6728178, rs6754295, rs673548, rs6711016, rs11902417, rs10184054, rs6544366, rs4564803, rs7557067, rs2678379, rs533617, rs679899, rs1801695, rs1367117, rs1042031. The association study between SNP and oxLDL level was performed by the ROC-analysis. Based on results, the group of SNP was selected. According to this group, the total SCORE (TS) showing the level of genetic susceptibility to an increased oxLDL level was calculated.Results. The present study included 717 patients ranging from 28 to 84 years old (with the median of 57), 204 men (28.45%). The oxLDL level varied from 21,03 to 163,72 U/dL (median 68,5) and correlated with the levels of total cholesterol (TC), triglycerides (TG), low density cholesterol (LDL-C), C-reactive protein (C-RP) and apolipoprotein B-100 (ApoB-100). The highest coefficients of correlations (p3 (p

Raman spectroscopic imaging was used to investigate the uptake of oxidized LDLs (oxLDLs) by human macrophages. To better understand the endocytic pathway and the intracellular fate of modified lipoproteins is of foremost interest with regard to the development of atherosclerotic plaques. To obtain information on the storage process of lipids caused by oxLDL uptake, Raman spectroscopic imaging was used because of its unique chemical specificity, especially for lipids. For the present study, a protocol was established to incorporate deuterated tripalmitate into oxLDL. Subsequently, human THP-1 macrophages were incubated for different time points and their chemical composition was analyzed using Raman spectroscopic imaging. β-Carotene was found to be a reliable marker molecule for the uptake of lipoproteins into macrophages. In addition, lipoprotein administration led to small endocytic vesicles with different concentrations of deuterated lipids within the cells. For the first time, the translocation of deuterated lipids from endocytic vesicles into lipid droplets over time is reported in mature human THP-1 macrophages.

Abstract Background Atherosclerosis is a common cardiovascular disease that causes myocardial infarction, heart failure, and stroke. Increased oxidized low density lipoprotein (ox-LDL) in the sub-endothelium is the characteristic origin of atherogenesis. Klotho, an anti-aging protein, has been reported to protect against atherosclerosis and ameliorate endothelial dysfunction in vivo. The aim of this study is to investigatethe anti-oxidative activity of Klothoin ox-LDL-treated human umbilical vein endothelial cells (HUVECs). Methods After pre-treatment with 200 pMKlotho for 1 h, HUVECs were stimulated with 50 μg/ml ox-LDL for 24 h. Reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were analyzed in the cells. Nitric oxide (NO) concertation was measured in the medium supernatant. Related proteins or genes were detected with Western blot or real time PCR, respectively, in the cell lysates. Results Initially, oxidative damage in HUVECs was established by adding 50 μg/mL ox-LDL, which resulted in decreased cellular viability, SOD/Cu/Zn-SOD and endothelial NO synthase (eNOS) expression and NO production, as well as increased malondialdehyde (MDA) levels, ROS production, inducible NO synthase (iNOS), phosphatidyl inositol-3 kinase (PI3K), protein kinase B (Akt), gp91 phox, and lectin-like ox-LDL receptor (LOX-1) expression in HUVECs. Pre-incubation with recombinant Klotho (200 pM) significantly prevented all of these alterations. These results suggest that Klotho can attenuate ox-LDL-induced oxidative stress in HUVECs through upregulating oxidative scavengers (SOD and NO) viaactivating the PI3K/Akt/eNOS pathway and depressing LOX-1expression. Conclusions These results suggest that Klotho has a potential therapeutic effect on attenuating endothelial dysfunction and ameliorating atherosclerosis.

Backgruound: Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes., Methods: We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin., Results: Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin., Conclusion: We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

Type 2 diabetes mellitus (T2DM) associated with reduced HDL-C level, induces change in HDL-C level, impairing cholesterol efflux and antioxidant capacity, which is associated with lower paraoxonase (PON1) protein expression and activity. This study aimed to assess PON1 activity in diabetic foot patients and explore the risk of cardiovascular disease. Iraqi patients with T2DM (n = 130) were enrolled after being divided into two groups; patients group with T2DM (n=22) and diabetic foot ulcer (DF) patients group (n = 108), which was classified to sub-groups according to Wagner classification. Also, a control group (n = 21) were used consisted of healthy subjects. Serum PON1 activity was measured using paraoxon as substrate. Oxidized low density lipoprotein (oxLDL) level was measured using ELISA kit. Results: The diabetic patients had significant lower paraoxonaseactivity, HDL-c level, while significantly higher levels of cholesterol, triglyceride, oxLDL, CRP, WBC was found when compared with control group. A significant negative correlation was found between PON1 activity and oxLDL level in patients groups. The increased oxLDL level and decreased PON1 activity in DF group is an indication of increased oxidative stress. Decrease activity of PON1 in DF group and its negative correlation with oxLDL level may increase their risk to CVD. [ABSTRACT FROM AUTHOR]

Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded. [ABSTRACT FROM AUTHOR]

Background/Aims: Atherosclerosis is a chronic inflammatory condition associated with a variety of vascular diseases. Previous studies showed that both miR-29a and oxidized low density lipoprotein (ox-LDL) were vital in the development of atherosclerosis. However, the relationship between miR-29a and ox-LDL remains unknown. This study was designed to investigate the association of miR-29a and ox-LDL and to test whether circulating miR-29a and ox-LDL levels could predict atherosclerosis. Methods: In 170 participants, plasma levels of miR-29a were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) while plasma ox-LDL levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. The relationship between miR-29a level and ox-LDL and carotid intima-media thickness (cIMT) was assessed using the Spearman correlation coefficient and multiple liner regression. Results: Compared with the normal cIMT group, the increased cIMT group had higher levels of ox-LDL (0.47 ± 0.08 vs 0.29 ± 0.06 ng/ml, p = 0.003) and miR-29a (32.93 ± 4.26 vs 26.37 ± 1.04, p p p Conclusion: Increased miR-29a and ox-LDL levels were associated with an early stage of atherosclerosis, and the combination of miR-29a and ox-LDL offered better predictive values for atherosclerosis than either alone.

Objectives: Psoriasis is a chronic inflammatory skin disease. Chronic inflammation results in increased oxidative stress and oxidizes lipoproteins, increasing their atherogenicity. This study sought to estimate the levels of oxidized low-density lipoprotein (ox-LDL) and antibodies against oxidized LDL (anti-ox-LDL) and compute the ratio of anti-ox-LDL/ox-LDL as a single composite parameter to assess the oxidative lipoprotein burden as an indicator of cardiovascular risk in patients with psoriasis. Methods: This cross-sectional study included 45 patients with psoriasis. All patients were given a psoriasis severity index score and their ox-LDL and anti-ox-LDL estimated using ELISA. Results: The results of this study show an elevation in the ratio of anti-ox-LDL to ox-LDL in patients with psoriasis, which initiate and perpetuate the pathogenesis of psoriasis and its comorbidity, atherosclerotic cardiovascular disease. Conclusions: Our results suggest that an elevated ratio of anti-ox-LDL/ox-LDL can serve as a composite parameter reflecting the total oxidative lipoprotein burden and cardiovascular risk in psoriasis patients.

Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism. We explored the effect of VNN1 on cholesterol metabolism, inflammation, apoptosis in vitro, and progression of atherosclerotic plaques in apoE−/− mice. Oxidized LDL (Ox-LDL) significantly induced VNN1 expression through an ERK1/2/cyclooxygenase-2/PPARα signaling pathway. VNN1 significantly increased cellular cholesterol content and decreased apoAI and HDL-cholesterol (HDL-C)-mediated efflux by 25.16% and 23.13%, respectively, in THP-1 macrophage-derived foam cells (P < 0.05). In addition, VNN1 attenuated Ox-LDL-induced apoptosis through upregulation of expression of p53 by 59.15% and downregulation of expression of B-cell lymphoma-2 127.13% in THP-1 macrophage (P < 0.05). In vivo, apoE−/− mice were divided randomly into two groups and transduced with lentivirus (LV)-Mock or LV-VNN1 for 12 weeks. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL-cholesterol (119.64%), TNF-α (148.74%), interleukin (IL)-1β (131.81%), and IL-6 (156.51%), whereas plasma levels of HDL-C (25.75%) were decreased significantly (P < 0.05). Consistent with these data, development of atherosclerotic lesions was increased significantly upon infection of apoE−/− mice with LV-VNN1. These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis.

Paeonol from Cortex Moutan root is a potential therapeutic agent for atherosclerosis (AS). However, its mechanisms of action are still not fully understood. Vascular endothelial cells (VECs) autophagy plays a vital role in the initiation and progression of AS. In this study, we aim to investigate whether the protective effect of paeonol on ox-LDL-induced VECs injury by regulating autophagy. To address this question, we used ox-LDL-induced rat VECs as a model system to elucidate the protective effect of paeonol on VECs injury. This study displayed that ox-LDL (100 mg/L) treatment inhibited VEC growth in dose- and time-dependent manners, paeonol (60 μM) shown potential in inhibiting ox-LDL-induced death. Furthermore, paeonol significantly reduced ox-LDL-induced the formation of autophagy vacuoles and the expression of LC3II in VECs. Further double-luciferase reporter assay shown that miR-30a specifically binds to the 3′-UTR of Beclin-1 mRNA in VECs. Moreover, we found that ox-LDL decreased miR-30a and increased Beclin-1 expression, pretreatment with paeonol could reverse the process of regulation in dose-dependent manners. In ox-LDL treated VECs, transfection with a miR-30a mimic significantly increased miR-30a expression and inhibited Beclin-1 and LC3II expression, thus enhanced the protective effects of paeonol. Whereas transfection with a miR-30a inhibitor significantly decreased miR-30a expression and increased Beclin-1 and LC3II expression, thus attenuated the protective effects of paeonol. In conclusion, this study has, for the ?rst time, highlighted that miR-30a might be a critical target of paeonol against ox-LDL-induced VECs injury by inhibiting excessive autophagy. Paeonol may be one of promising candidate drug for treatment of AS.