LDL Oxidation Research Articles

Kinetics of lipid radical formation in lipoproteins from β-thalassemia: Implication of cholesteryl esters and α-tocopherol

Vascular complications in β-thalassemia are associated with oxidative modification of lipoproteins under high oxidative stress. The lipid components of lipoproteins are oxidized via lipid peroxidation and produce lipid radicals (L•) as the key initial intermediates. Modification of lipid components, therefore, might result in alterations in the rate and products of lipid peroxidation. In this study, the kinetics of L• formation during the 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH)- and hemin-induced oxidation of low-density and high-density lipoproteins (LDL and HDL) from β-thalassemia patients and healthy volunteers were investigated using a specific and sensitive fluorescence probe for L•. Kinetic parameters, including initial lag time, propagation rate and total L• production, were calculated by monitoring a fluorescence-active NBD-Pen-L• adduct. Oxidation of thalassemia lipoproteins exhibited a significantly shorter lag time but a slower propagation rate of L• formation when compared with healthy lipoproteins. LDL showed higher resistance to oxidation during the initiation phase but higher L• formation than HDL. Our results indicated that the levels of α-tocopherol determined the initial lag time, whereas the levels of core lipids and cholesteryl esters, especially cholesteryl linoleate (CL), determined the propagation rate and total L• production. The difference in potency of AAPH and hemin supported that hemin preferentially targeted core lipids. Moreover, analysis of 13-hydroxyoctadecadienoic acid cholesteryl ester (13-HODE-CE)/CE ratio indicated that thalassemia lipoproteins have higher susceptibility to oxidation than healthy lipoproteins. In conclusion, our findings suggested that CL and α-tocopherol were implicated in the susceptibility of lipoproteins to lipid peroxidation in physiological and pathological conditions of β-thalassemia.

Effects of Coconut Oil on Weight Loss and Blood Lipids

Hindistan cevizi yağı tropikal ülkelerde binlerce yıldır kullanılan, Cocos nucifera adlı ağaçtan elde edilen yenilebilir bir yağdır. Saf hindistan cevizi yağı, hindistan cevizinin taze, olgun çekirdeğinden, mekanik veya doğal yollarla, ısı kullanılarak veya kullanılmadan kimyasal rafinasyon işlemi yapılmadan elde edilir. Hindistan cevizi yağı esas olarak 6-12 karbon atomundan oluşan orta zincirli yağ asitlerinden (MCT) oluşur. Hindistan cevizi yağının ağırlık kaybı üzerindeki etkilerinin termogenezi ve doygunluk yanıtını artırmasından kaynaklı olduğu bildirilmektedir. Sızma hindistan cevizi yağının kan lipidleri ve LDL oksidasyonu üzerindeki potansiyel yararlı etkilerinin ise, içerdiği biyoaktif polifenol bileşenlerden kaynaklandığı düşünülmektedir. Bu derleme, son yıllarda sağlık faydaları ile ön plana çıkan hindistan cevizi yağının ağırlık kaybı ve kan lipidleri üzerindeki etkilerine güncel bir bakış sunmaktadır.

MAGI1 inhibits interferon signaling to promote influenza A infection.

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may promote IAV infection. Treatment of ECs with oxidized low-density lipoprotein (OxLDL) increases MAGI1 expression and IAV infection, suggesting that MAGI1 is part of the mechanistic link between serum lipid levels and patient prognosis following IAV infection. Our microarray studies suggest that MAGI1-depleted ECs increase protein expression and signaling networks involve in interferon (IFN) production. Specifically, infection of MAGI1-null ECs with IAV upregulates expression of signal transducer and activator of transcription 1 (STAT1), interferon b1 (IFNb1), myxovirus resistance protein 1 (MX1) and 2′-5′-oligoadenylate synthetase 2 (OAS2), and activate STAT5. By contrast, MAGI1 overexpression inhibits Ifnb1 mRNA and MX1 expression, again supporting the pro-viral response mediated by MAGI1. MAGI1 depletion induces the expression of MX1 and virus suppression. The data suggests that IAV suppression by MAGI1 depletion may, in part, be due to MX1 induction. Lastly, interferon regulatory factor 3 (IRF3) translocates to the nucleus in the absence of IRF3 phosphorylation, and IRF3 SUMOylation is abolished in MAGI1-depleted ECs. The data suggests that MAGI1 inhibits IRF3 activation by maintaining IRF3 SUMOylation. In summary, IAV infection occurs in ECs in a MAGI1 expression-dependent manner by inhibiting anti-viral responses including STATs and IRF3 activation and subsequent MX1 induction, and MAGI1 plays a role in EC activation, and in upregulating a pro-viral response. Therefore, the inhibition of MAGI1 is a potential therapeutic target for IAV-induced cardiovascular disease.

Vertebral Artery Stenosis: A Narrative Review

Vertebral artery stenosis (VAS) is the cause of approximately 20% of ischemic strokes in the posterior circulation. There are several causes of vertebral artery stenosis, including atherosclerosis, calcification, dissections, fibromuscular dysplasia, giant cell arteritis, neurofibromatosis type 1, and bony compressions. The most common cause of VAS is atherosclerosis which is derived from the macrophage-induced oxidation of low-density lipoproteins (LDLs), alongside the accumulation of cholesterol. Calcification of the vertebral artery occurs when there is excess calcium and phosphate deposition in the vessel. Dissection of the vertebral artery can lead to the formation of a hematoma causing stenosis of the vertebral artery. Fibromuscular dysplasia can result in stenosis due to the deposition of collagen fibers in the tunica media, intima, or adventitia. Giant cell arteritis, an autoimmune disorder, causes inflammation of the internal elastic membrane resulting in eventual stenosis of the artery. Neurofibromatosis type 1, an autosomal dominant disorder, results in the stenosis of the vertebral artery due to the altered function of neurofibromin. Mechanical compression of the vertebral artery by bone can also cause stenosis of the vertebral artery. Digital subtraction angiography (DSA) is considered the current gold standard in diagnosing vertebral artery stenosis; however, its associated morbidity and mortality have led to increased use of non-invasive techniques such as duplex ultrasonography (DUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). Currently, asymptomatic and symptomatic vertebral artery stenoses are treated by risk factor modification and medical treatment. However, it is recommended that surgical (endarterectomy, reconstruction, and decompression) and endovascular (balloon coronary, bare-metal, and drug-eluting stents) treatments are also used for symptomatic vertebral artery stenosis.

Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model.

High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10 days. Then, they randomly received one of the 30-day interventions: (I) hypercholesterolemic (HC) diet; (II) HC diet + rosuvastatin; (III) normocholesterolemic (NC) diet; (IV) NC diet + rosuvastatin. We determined cholesterol efflux capacity (CEC), antioxidant potential, HDL particle number, HDL apolipoprotein content, LDL oxidation, and lipid levels. Hypercholesterolemia time-dependently impaired HDL function (−62% CEC, −11% antioxidant index (AOI); p < 0.01), increased HDL particles numbers 2.8-fold (p < 0.0001), reduced HDL-bound APOM (−23%; p < 0.0001), and increased LDL oxidation 1.7-fold (p < 0.0001). These parameters remained unchanged in animals on HC diet alone up to day 40, while AOI deteriorated up to day 25 (−30%). The switch to NC diet reversed HDL dysfunction, restored apolipoprotein M content and particle numbers, and normalized cholesterol levels at day 40. Rosuvastatin improved HDL, AOI, and apolipoprotein M content. Apolipoprotein A-I and apolipoprotein C-III remained unchanged. Lowering LDL-C levels with a low-fat diet rescues HDL CEC and antioxidant potential, while the addition of rosuvastatin enhances HDL antioxidant capacity in a pig model of hypercholesterolemia. Both strategies restore HDL-bound apolipoprotein M content.

Antioxidant and anti-inflammatory effects of Rosmarinus officinalis and Melissa officinalis ethanolic extracts

Background and Aims : Oxidized LDL, endothelial dysfunction and neutrophil extracellular trap formation (NETs) play a central role in atherosclerosis. The aim of the present study was to investigate the effect of Rosmarinus officinalis (ROe) and Melissa officinalis (MOe) ethanolic extracts on LDL oxidation, intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells (HUVECs) and NET formation.Methods: Ethanolic extraction of whole plants was performed for 72h. Phytochemical analysis was performed using NMR-spectroscopy. LDL (d=1.019-1.063g/mL) was isolated by sequential ultracentrifugation of plasma from healthy volunteers and oxidized (100μg protein/mL) by 5μM CuSO4, in the presence of ROe or MOe, for 6h. HUVECs were pre-incubated with various extract concentrations for 1h and treated with 0.5ng/mL TNF-α for 6h or 8U/mL thrombin for 24h. ICAM-1 expression was determined by flow cytometry. Neutrophils (2×105) were isolated, pre-incubated with the extracts for 5min and activated with 100nM PMA for 4h at 37°C, 5% CO2. NETs were isolated and quantitated using ELISA kit.Conclusions: ROe and MOe share many similarities in their phytochemical profile, however ROe exhibits more potent antioxidant activity than MOe and anti-inflammatory activities that are not present in MOe. Further ongoing studies will shed light into the active compounds of ROe and their specific mechanisms of action. Background and Aims : Oxidized LDL, endothelial dysfunction and neutrophil extracellular trap formation (NETs) play a central role in atherosclerosis. The aim of the present study was to investigate the effect of Rosmarinus officinalis (ROe) and Melissa officinalis (MOe) ethanolic extracts on LDL oxidation, intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells (HUVECs) and NET formation. Methods: Ethanolic extraction of whole plants was performed for 72h. Phytochemical analysis was performed using NMR-spectroscopy. LDL (d=1.019-1.063g/mL) was isolated by sequential ultracentrifugation of plasma from healthy volunteers and oxidized (100μg protein/mL) by 5μM CuSO4, in the presence of ROe or MOe, for 6h. HUVECs were pre-incubated with various extract concentrations for 1h and treated with 0.5ng/mL TNF-α for 6h or 8U/mL thrombin for 24h. ICAM-1 expression was determined by flow cytometry. Neutrophils (2×105) were isolated, pre-incubated with the extracts for 5min and activated with 100nM PMA for 4h at 37°C, 5% CO2. NETs were isolated and quantitated using ELISA kit. Conclusions: ROe and MOe share many similarities in their phytochemical profile, however ROe exhibits more potent antioxidant activity than MOe and anti-inflammatory activities that are not present in MOe. Further ongoing studies will shed light into the active compounds of ROe and their specific mechanisms of action.

Investigation of the antioxidant and anti-inflammatory potency of Echinacea angustifolia extract

Background and Aims : Echinacea is known for its potent antioxidant properties. We studied the effect of 2 different extracts of Echinacea angustifolia on low-density lipoprotein (LDL) oxidation and on the expression of the adhesion molecule ICAM-1, on endothelial cells (HUVECs) activated with the tumor necrosis factor-alpha (TNF-α).

CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes

The mechanisms that control the inflammatory–immune response play a key role in tissue remodelling in cardiovascular diseases. T cell activation receptor CD69 binds to oxidized low-density lipoprotein (oxLDL), inducing the expression of anti-inflammatory NR4A nuclear receptors and modulating inflammation in atherosclerosis. To understand the downstream T cell responses triggered by the CD69-oxLDL binding, we incubated CD69-expressing Jurkat T cells with oxLDL. RNA sequencing revealed a differential gene expression profile dependent on the presence of CD69 and the degree of LDL oxidation. CD69-oxLDL binding induced the expression of NR4A receptors (NR4A1 and NR4A3), but also of PD-1. These results were confirmed using oxLDL and a monoclonal antibody against CD69 in CD69-expressing Jurkat and primary CD4 + lymphocytes. CD69-mediated induction of PD-1 and NR4A3 was dependent on NFAT activation. Silencing NR4A3 slightly increased PD-1 levels, suggesting a potential regulation of PD-1 by this receptor. Moreover, expression of PD-1, CD69 and NR4A3 was increased in human arteries with chronic inflammation compared to healthy controls, with a strong correlation between PD-1 and CD69 mRNA expression (r = 0.655 P < 0.0001). Moreover, PD-1 was expressed in areas enriched in CD3 infiltrating T cells. Our results underscore a novel mechanism of PD-1 induction independent of TCR signalling that might contribute to the role of CD69 in the modulation of inflammation and vascular remodelling in cardiovascular diseases.

Assessment of oxidative and cardiovascular changes in pregnant women attending antenatal clinic at Federal Medical Centre, Owerri Nigeria

Background: In pregnancy which is a physiological state that is accompanied by high energy demand, there is an increased intake and utilization of oxygen, hence augmented levels of oxidative changes that are associated with a lot of risks, one of which is cardiovascular diseases. This research aims to investigate the oxidative changes that occur among pregnant women by determining the levels of High Sensitivity c-Reactive Protein (hs-CRP) and Oxidized Low-Density Lipoprotein (OxLDL) in first, second and third trimesters. Materials and Methodology: A total of 60 pregnant women were recruited for the study. Twenty (20) pregnant women each from the three trimesters while Twenty (20) non-pregnant pubertal women without any chronic disease were used as control. 5ml of venous blood was collected from all subjects and analyzed for OxLDL and hs-CRP using an Enzyme-Linked Immunosorbent Assay (ELISA) technique. The data were analyzed using Statistical Package for the Social Sciences (SPSS) version 18. Results: Oxidized Low-Density Lipoprotein (OxLDL) showed mean variations across the groups but was not significant (P&gt;0.05) but Pregnant women in their second trimester showed significant mean variation (P&lt;0.05) (3716.11±599.86) in when compared to non-pregnant women (control) (4305.33±68.90) respectively. Pregnant women in the second trimester showed significantly decreased mean variation (P&lt;0.05) in High sensitivity C-reactive protein (85.09 ±12.38) when compared to non-pregnant women (control) (219.45 ±64.61) respectively. Conclusions: This study shows that there are increases in levels of OxLDL and a decrease in plasma concentration of hs-CRP which are more significant in the second trimester.

Functional food in the primary prevention of cardiovascular diseases

Cardiovascular diseases, metabolic disorders and obesity are a serious threat to civilization, especially in highly developed countries. Due to the number of deaths and complications they are among the health priorities in Poland. The aim of the study is to review the literature on the role of functional food in the primary prevention of cardiovascular diseases. Functional food, thanks to its antioxidant, hypocholesterolemic and anti-inflammatory properties, has a beneficial effect on lowering blood pressure, cholesterol levels, inhibiting LDL oxidation or inhibiting platelet aggregation. It is necessary to promote this type of food, because its action has a significant impact on the prevention of various diseases, especially cardiovascular, diet-related and civilization. Proper nutritional education is a way to improve human potential and health. Therefore, it is worth educating in order to promote these products and increase the interest in them as well as raise the nutritional awareness of the society.

Lysophosphatidylcholine: Potential Target for the Treatment of Chronic Pain.

The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of phosphatidylcholine by phospholipase A2 (PLA2) and is catabolized to other substances by different enzymatic pathways. LPC exerts pleiotropic effects mediated by its receptors, G protein-coupled signaling receptors, Toll-like receptors, and ion channels to activate several second messengers. Lysophosphatidylcholine (LPC) is increasingly considered a key marker/factor positively in pathological states, especially inflammation and atherosclerosis development. Current studies have indicated that the injury of nervous tissues promotes oxidative stress and lipid peroxidation, as well as excessive accumulation of LPC, enhancing the membrane hyperexcitability to induce chronic pain, which may be recognized as one of the hallmarks of chronic pain. However, findings from lipidomic studies of LPC have been lacking in the context of chronic pain. In this review, we focus in some detail on LPC sources, biochemical pathways, and the signal-transduction system. Moreover, we outline the detection methods of LPC for accurate analysis of each individual LPC species and reveal the pathophysiological implication of LPC in chronic pain, which makes it an interesting target for biomarkers and the development of medicine regarding chronic pain.

Circ_0093887 regulated ox-LDL induced human aortic endothelial cells viability, apoptosis, and inflammation through modulating miR-758-3p/BAMBI axis in atherosclerosis.

Compelling evidence demonstrated that circular RNAs (circRNAs) were involved in the progression of atherosclerosis (AS). However, the role of circ_0093887 in the progression of AS is unclear. The purpose of this study was to explore the role and mechanism of circ_0093887 in oxidized-low density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs). HAECs were stimulated by ox-LDL to simulate AS-like injury in vitro. Circ_0093887, microRNA-758-3p (miR-758-3p), and BMP And Activin Membrane-Bound Inhibitor (BAMBI) levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). PCNA, Bax, Bcl-2, and BAMBI protein levels were detected by western blot. Cell viability and apoptosis were examined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Tube formation assay was used to assess tube formation. The levels of inflammatory factors TNF-α and IL-1β were detected by corresponding ELISA kits. The relationship between miR-758-3p and circ_0093887 or BAMBI was tested via dual-luciferase reporter analysis and RNA immunoprecipitation. Oxidative stress related indexes (ROS and MDA) were detected by corresponding kits. The expression levels of circ_0093887 and BAMBI were prominently downregulated in ox-LDL-induced HAECs compared with control, whereas the expression of miR-758-3p was upregulated. Overexpression of circ_0093887 promoted HAECs viability and tube formation, and restrained cell apoptosis in ox-LDL-induced HAECs compared with untreated HAECs. Mechanistically, circ_0093887 regulated the expression of BAMBI through miR-758-3p. Further experiments showed that upregulation of miR-758-3p reversed changes in cell function induced by circ_0093887. In addition, reduced BAMBI salvaged miR-758-3p knockdown mediated effects on cell function. Circ_0093887 demonstrated its diagnostic and therapeutic value in AS by promoting the role of the miR-758-3p/BAMBI axis in the ox-LDL-induced endothelial injury of HAECs.

LRPPRC inhibits autophagy and promotes foam cell formation in atherosclerosis.

Lipid-laden macrophages are considered as the main source of foam cells in atherosclerosis; however, the mechanism for macrophage foam cell formation remains unknown. Here, we explore the mechanism behind foam cell formation to potentially identify a novel treatment for atherosclerosis. Our data demonstrated that leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) increased in the atherosclerotic plaques of LDLR-/- mice fed with a Western diet. LRPPRC was also upregulated in mice peritoneal macrophages and RAW 264.7 cells treated with oxidative low density lipoprotein, whereas knockdown of LRPPRC by transfecting with small interfering (Si)-LRPPRC in RAW 264.7 cells decreased foam cell formation. Furthermore, Si-LRPPRC promoted autophagy and increased the expression of cholesterol efflux protein ATP-binding cassette transporter A1 in RAW 264.7 cells. Moreover, intervention with MHY1485 in RAW 264.7 cells revealed that autophagy was inhibited by LRPPRC via the Akt-mechanistic target of rapamycin pathway. Taken together, we confirm for the first time that LRPPRC is increased within the atherosclerotic plaques of mice and enhances the process of foam cell formation. The knockdown of LRPPRC inhibited foam cell formation by activating macrophage autophagy. Our findings indicate that the regulation of macrophage LRPPRC expression may be a novel strategy for ameliorating atherosclerosis.

The effect of squalene on lipid profile and some oxidative biomarkers in patients with type 2 diabetes mellitus

Background: Squalene, as an isoprene, is one of the components of amaranth oil and makes up about 8% of this oil. Squalene has anti-inflammatory and antioxidant effects that have been considered in many studies. In people with uncontrolled diabetes, there is an increase in total cholesterol and low-density lipoprotein (LDL) alongside a decrease in high-density lipoproteins (HDL).According to studies, squalene can be useful in lowering total cholesterol and triacylglycerol.Objective: The aim of this study was to investigate whether squalene has an effect on lipid profile and a number of oxidative biomarkers in patients with type 2 diabetes.Methods: In the present study, 30 healthy volunteers were selected as the control group and 120 volunteers with type 2 diabetes mellitus (T2DM) were selected. Subjects with diabetes were randomly divided into 4 groups. Group 1 was untreated with squalene and groups 3, 4, and 5 were treated with different doses of squalene for 84 days. Lipid profiles and oxidant biomarkers were examined on days 1, 14, 28, 56, and 84 according to the relevant protocols in all groups.Results: Significant differences (P &lt; 0.05) were observed between control and diabetic groups in the study of cholesterol, triglycerides, LDL, HDL, very low-density lipoproteins (VLDL), oxidized low-density lipoprotein (Ox-LDL), and malondialdehyde. There was a significant difference between the studied groups in the levels of parameters expressed in some different doses and days.At the levels of the parameters expressed in some doses and different days, a significant difference was observed between the groups treated and untreated with squalene.Conclusion: This study shows that squalene as a bioactive compound can be effective to manage certain symptoms of diabetics including HDL, LDL, total cholesterol, and VLDL. From our findings, we observed that squalene consumption over the duration of 84 days resulted in increased levels of HDL in diabetic patients. It also resulted in decreased levels of total cholesterol, LDL, and VLDL in diabetic patients. Keywords: Squalene, lipid profile, oxidative biomarkers, diabetes mellitus

The Benefits of High-Resistant Starch and Beta-Carotene Snack in Ameliorating Atherogenic Index and Inflammation in Obesity

BACKGROUND: In obesity, lipid abnormalities may be related to the higher risk of cardiovascular diseases associated with increased oxidation of lipids and inflammation. Resistant starch and beta-carotene reduce atherosclerosis risk related to low-grade inflammation and oxidative stress in obesity. AIM: This study aimed to evaluate the benefits of a snack containing high-resistant starch and beta-carotene in improving the atherogenic index of plasma (AIP) and inflammation in obesity. METHODS: This study used a single-blinded and randomized controlled design. Fifty subjects received 42 g of snacks per day for 6 weeks, either tested snacks or standard snacks. Anthropometry, body composition, lipid profile, tumor necrosis factor-alpha (TNF-α), and oxidized low-density lipoprotein (ox-LDL) were measured before and after intervention. RESULTS: The snack containing high-resistant starch and beta-carotene significantly decreased LDL, AIP, and TNF-α (p &lt; 0.05). Positive correlations were found between AIP and triglycerides in both snacks (p &lt; 0.05), LDL or TNF-α in the standard snack (p &lt; 0.05), and TNF-α and ox-LDL in both snacks (p &lt; 0.05). A negative correlation was found between AIP and HDL in both snacks (p &lt; 0.05). CONCLUSIONS: A snack containing high-resistant starch and beta-carotene reduced AIP and inflammation by preventing LDL oxidation.

Enzymatic Synthesis and Antioxidant Activity of Mono- and Diacylated Epigallocatechin Gallate and Related By-Products.

Ester derivatives of epigallocatechin gallate (EGCG) were enzymatically prepared by one-step transesterification with vinyl fatty acids consisting of varying acyl groups ranging from 2 to 18 carbon atoms (acetate, butyrate, caproate, caprylate, caprate, laurate, myristate, and stearate). The main acylation products were EGCG monoesters and diesters. However, due to the presence of trace amounts of water in the reaction medium, minor but noticeable hydrolysis of EGCG also occurred as a side reaction which required a prolonged purification process due to the formation of by-products such as gallic acid, epigallocatechin, and their esters. In this contribution, 8 EGCG monoesters, 7 EGCG diesters, and 7 gallic acid monoesters were isolated and purified, and the acylation positions were characterized. Meanwhile, several classical chemicals (DPPH, ABTS, FRAP, and Fe2+ chelation assays), food (β-carotene bleaching assay), and biological (LDL and DNA oxidation assays) models were conducted to evaluate and systematically compare their antioxidant efficacy. The lipophilicity of the EGCG derivatives increased with the increasing chain length of the acyl group and led to the fluctuation of their antioxidant efficacies. Three main factors, namely, the reduction potential, the partition coefficient of solute in the solvent system, and the steric hindrance of antioxidant agent and related substrates were considered to help explain the biased antioxidant performance of EGCG derivatives upon acylation modification. The results strongly suggest that the acylated EGCGs have great potential as lipophilic alternatives to the water-soluble EGCG in lipid-based matrices.

Serum cholesterol loading capacity of macrophages is regulated by seropositivity and C-reactive protein in rheumatoid arthritis patients.

Excessive cholesterol accumulation in macrophages is the pivotal step underlying atherosclerotic plaque formation. We here explore factors in the serum of patients with RA, and mechanisms through which they interact with and influence cholesterol loading capacity (CLC) of macrophages. In a cross-sectional observational cohort of 104 patients with RA, CLC was measured as intracellular cholesterol content in human THP-1-derived macrophages after incubation with patient serum. Low-density lipoprotein (LDL) oxidation was measured in terms of oxidized phospholipids on apoB100-containing particles (oxPL-apoB100). Antibodies against oxidized LDL (anti-oxLDL), proprotein convertase subtilisin/Kexin type-9 (PCSK9) and high-sensitivity CRP were also quantified. All analyses adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, obesity, total LDL, statin use, age at diagnosis, and anti-oxLDL IgM. OxPL-apoB100, anti-oxLDL IgG and PCSK9 were positively associated with CLC (all P < 0.020). OxPL-apoB100 directly influenced CLC only in dual RF- and ACPA-positive patients [unstandardized b (95% bootstrap CI)=2.08 (0.38, 3.79)]. An indirect effect of oxPL-apoB100 on CLC through anti-oxLDL IgG increased, along with level of CRP [index of moderated mediation = 0.55 (0.05-1.17)]. CRP also moderated yet another indirect effect of oxPL-apoB100 on CLC through upregulation of PCSK9, but only among dual-seropositive patients [conditional indirect effect = 0.64 (0.13-1.30)]. Oxidized LDL can directly influence CLC in dual-seropositive RA patients. Two additional and independent pathways-via anti-oxLDL IgG and PCSK9-may mediate the effects of oxPL-apoB100 on CLC, depending on CRP and seropositivity status. If externally validated, these findings may have clinical implications for cardiovascular risk prevention.

Prevention and Treatment of Cardiovascular Diseases with Plant Phytochemicals: A Review.

Cardiovascular diseases (CVDs) are the world's leading killers, accounting for 30% deaths. According to the WHO report, CVDs kill 17.9 million people per year, and there will be 22.2 million deaths from CVD in 2030. The death rates rise as people get older. Regarding gender, the death rate of women by CVD (51%) is higher than that of men (42%). To decrease and prevent CVD, most people rely on traditional medicine originating from the plant (phytochemicals) in addition to or in preference to commercially available drugs to recover from their illness. The CVD therapy efficacy of 92 plants, including 15 terrestrial plants, is examined. Some medicinal plants well known to treat CVD are, Daucus carota, Nerium oleander, Amaranthus Viridis, Ginkgo biloba, Terminalia arjuna, Picrorhiza kurroa, Salvia miltiorrhiza, Tinospora cordifolia, Mucuna pruriens, Hydrocotyle asiatica, Bombax ceiba, and Andrographis paniculate. The active phytochemicals found in these plants are flavonoids, polyphenols, plant sterol, plant sulphur compounds, and terpenoids. A general flavonoid mechanism of action is to prevent low-density lipoprotein oxidation, which promotes vasodilatation. Plant sterols prevent CVD by decreasing cholesterol absorption in the blood. Plant sulphur compound also prevent CVD by activation of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and inhibition of cholesterol synthesis. Quinone decreases the risk of CVD by increasing ATP production in mitochondria while terpenoids by decreasing atherosclerotic lesion in the aortic valve. Although several physiologically active compounds with recognized biological effects have been found in various plants because of the increased prevalence of CVD, appropriate CVD prevention and treatment measures are required. More research is needed to understand the mechanism and specific plants' phytochemicals responsible for treating CVD.

LDL oxydées et récepteur des LDL oxydées associés à la proprotéine-convertase-subtilisine/kexine type 9 chez des patients avec diabète de type 2

AbstractProprotein Convertase Subtilisin/Kexin type 9 (PCSK9) plays a key role in the regulation of lipid metabolism, in inflammatory response and in the development of atherosclerosis. We evaluated plasma PCSK9 levels in Tunisian patients with type 2 diabetes mellitus (T2DM) and investigated its association with oxidized-LDL (Ox-LDL) and Lectin-Like Oxidized LDL Receptor-1 (LOX-1 ). Plasma PCSK9, Ox- LDL and LOX-1 levels were measured in a Tunisian cohort of patients with T2DM (n = 50) compared to an age- and gender-matched control group (n = 50). Plasma levels of PCSK9, Ox-LDL and LOX-1 were significantly higher in T2DM patients compared to controls (p < 0.0001). Univariate regression analysis showed that the plasma level of PCSK9 was positively associated to Ox-LDL and LOX-1 levels in diabetic patients (p = 0.004 ; p = 0.012; respectively); however, no-independent association was found after multiple linear regression analysis between those parameters. Our data showed that PCSK9 was positively associated to Ox-LDL and LOX-1 showing as specific regulation between the oxidative parameters and an enzyme regulating lipid metabolism. These results attest the impact of PCSK9 to develop atherosclerosis in T2DM in a Tunisian cohort. Finally, PCSK-9 could be a new marker of the development of atherosclerosis in diabetic patients.

EFFECTS OF RESVERATROL ON HUMAN HEALTH

Grape is a perennial plant and its fruit and leaves are consumed as food. Its homeland is thought to be the Middle East. There is evidence that the cultivation of this plant began 7-8 thousand years ago. When we look at the content of ripe grapes, 100 grams of grapes contain 69 kilos of energy, 81% of them are water, 18% are carbohydrates, 1% is protein, and contain very little fat, vitamin K and vitamin E. Resveratrol (RSV) was first produced in the early 1930s by the medicinal plant Veratrum grandifolium Loes. fil., many studies have shown that it will be useful in clinical use due to the flavonoids and polyphenolic compounds found in grapes. RSV is a natural non-flavonoid polyphenol belonging to the stilbenoid group, especially found in the skin of black grapes. Besides grapes, it is also found in various plants such as strawberries, blueberries, pomegranates, mulberries, pistachios and peanuts. It is thought that RSV, which is found in dietary components, may have many effects such as antioxidant, anti-inflammatory, anticarcinogenic, neuroprotective, cardioprotective, lipid regulating, antidiabetic and life-prolonging. The potential benefits of RSV have been widely studied in some animal experiments, with positive results. Clinical trials in humans, on the other hand, are less numerous and the results are not yet conclusive. Considering the scientific studies done so far, it has been determined that RSV has tumor-suppressive properties in many stages of cancer. It is a powerful antioxidant that can prevent cell damage caused by free radicals. Radiotherapy or chemotherapy causes inflammation in neighboring cells of cancer cells, while RSV stimulates leukocytes to eliminate these lysed cells, thereby accelerating their apoptosis. RSV improves lipid profile by reducing hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase in mRNA expression and potentially leading to reverse cholesterol transport. It has been shown that it can lower blood pressure by increasing endothelial nitric oxide (NO) production, reducing oxidative damage and calcium influx. While RSV does not cause any changes in blood pressure acutely, when used for a long time, it improves endothelial function, especially in hypertensive women with higher LDL cholesterol levels. Because polyphenols reduce atherogenesis by preventing low-density lipoprotein oxidation, fat accumulation and platelet aggregation. Down-regulation of inflammatory pathways and regular signaling, decrease in IL-6, TNF alpha, interferon-gamma, Herp, IL-8 and leptin levels, down-regulation of leukocyte adhesion molecules, changes in mRNAs involved in inflammatory modulation, anti-inflammatory effect through an increase in IL-10 plasma levels shows. Recent studies have shown that RSV has a curative effect on Alzheimer's disease and prevents neurological damage in case of cerebral ischemia. It has a protective effect against chronic obstructive pulmonary disease. Some recent studies on RSV have determined that it prolongs lifespan in some yeasts, threadworms, fruit flies, fish, and obese mice. Keywords: Grape seeds, antioxidant, effects of resveratrol.