LDL Oxidation Research Articles

We Must Abandon the Myth: Oxidized Low-density Lipoprotein is not a Lipoprotein that Plays a Key Role in Atherogenesis.

The purpose of this review is to revisit in detail the arguments supporting or disproving the hypothesis that oxidized low-density lipoprotein (LDL) plays a key role in atherosclerotic lesion development. The detection of oxidized LDL in vivo was extremely important for confirming its key role in atherogenesis. Indirect evidence of its existence included the presence of autoantibodies against malondialdehyde-treated LDL in human blood; however, the affinity of circulating antibodies to another LDL modification, such as desialylated LDL, was an order of magnitude stronger. At least 3 forms of atherogenic modified lipoproteins were isolated from the blood of atherosclerotic patients using different methods, namely, small dense, electronegative and desialylated. Their properties were so similar that it was suggested that the three types could be classified as the same multiple-modified LDL particle. It has been shown that when native (unmodified) LDL is incubated with autologous serum from patients with atherosclerosis, multiple modifications occur, which include desialylation, a decrease in the content of phospholipids and neutral lipids, a decrease in particle size, an increase in negative charge and other physical and chemical changes. Longer incubation also increased the susceptibility of LDL to oxidation. Thus, LDL oxidation is not the only, much less the most important, form of atherogenic modification of LDL since it occurs at the last stages of multiple modifications cascade and does not significantly increase the atherogenic potential of multiple-modified LDL. Finally, clinical trials did not support the oxidative hypothesis; however, research on oxidized LDL continues, influencing the future research. It is time to abandon the myth!

Yerba Mate as a Protectant against Lipoproteins Oxidation.

Oxidative modification of low-density lipoproteins (LDL) and high-density lipoproteins (HDL) are important factors determining cardiovascular risk. This study investigated the antioxidant mechanisms and potential protective effect of a hydroethanolic extract of yerba mate (Ilex paraguaiensis; EHEM) on the in vitro oxidation of LDL and HDL. EHEM was found to possess ferric reducing power, DPPH free radical scavenging capacity, metal chelating activity, and NO radical scavenging activity. In addition, EHEM reduced the lipoperoxidation induced by α,α'-Azodiisobutyramidine dihydrochloride (AAPH) in HDL and LDL at all tested concentrations. In this study, we demonstrate the antioxidant properties of yerba mate and its phytochemical compounds. These properties may effectively prevent the in vitro oxidation of LDL and HDL molecules, a phenomenon linked to the pathogenesis of atherosclerosis.

Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1

Atherosclerosis results from the deposition and oxidation of LDL and immune cell infiltration in the sub-arterial space leading to arterial occlusion. Studies have shown that transcytosis transports circulating LDL across endothelial cells lining blood vessels. LDL transcytosis is initiated by binding to either scavenger receptor B1 (SR-B1) or activin A receptor-like kinase 1 on the apical side of endothelial cells leading to its transit and release on the basolateral side. HDL is thought to partly protect individuals from atherosclerosis due to its ability to remove excess cholesterol and act as an antioxidant. Apolipoprotein A1 (APOA1), an HDL constituent, can bind to SR-B1, raising the possibility that APOA1/HDL can compete with LDL for SR-B1 binding, thereby limiting LDL deposition in the sub-arterial space. To examine this possibility, we used in vitro approaches to quantify the internalization and transcytosis of fluorescent LDL in coronary endothelial cells. Using microscale thermophoresis and affinity capture, we find that SR-B1 and APOA1 interact and that binding is enhanced when using the cardioprotective variant of APOA1 termed Milano (APOA1-Milano). In male mice, transiently increasing the levels of HDL reduced the acute deposition of fluorescently labeled LDL in the atheroprone inner curvature of the aorta. Reduced LDL deposition was also observed when increasing circulating wild-type APOA1 or the APOA1-Milano variant, with a more robust inhibition from the APOA1-Milano. The results suggest that HDL may limit SR-B1-mediated LDL transcytosis and deposition, adding to the mechanisms by which it can act as an atheroprotective particle.

Quercetin, a Flavonoid with Great Pharmacological Capacity.

Quercetin is a flavonoid with a low molecular weight that belongs to the human diet's phenolic phytochemicals and nonenergy constituents. Quercetin has a potent antioxidant capacity, being able to capture reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive chlorine species (ROC), which act as reducing agents by chelating transition-metal ions. Its structure has five functional hydroxyl groups, which work as electron donors and are responsible for capturing free radicals. In addition to its antioxidant capacity, different pharmacological properties of quercetin have been described, such as carcinostatic properties; antiviral, antihypertensive, and anti-inflammatory properties; the ability to protect low-density lipoprotein (LDL) oxidation, and the ability to inhibit angiogenesis; these are developed in this review.

MiR-2467-3p/ABLIM1 Axis Mediates the Formation and Progression of Deep Vein Thrombosis by Regulating Inflammation and Oxidative Stress.

Deep vein thrombosis (DVT) is a common postoperative complication of orthopaedic surgery with a complex pathogenesis mechanism. The effect of the miR-2467-3p/acting-binding LIM protein 1 (ABLIM1) axis on thrombus formation and human vascular endothelial cells (HUVECs) progression was evaluated aiming to identify a novel potential biomarker of DVT. DVT rat models were established by inferior vena cava stenosis. The expression of the miR-2467-3p/ABLIM1 axis was analyzed by PCR. HUVECs were induced with oxidative low-density lipoprotein (ox-LDL). Cell growth and motility were assessed by cell counting kit 8 (CCK8) and Transwell assay. The inflammation and oxidative stress were estimated by proinflammatory cytokines and generation of MDA and reactive oxygen species (ROS). ABLIM1 was downregulated in DVT rats. Overexpressing ABLIM1 could suppress the formation of thrombosis and alleviate inflammation and oxidative stress. In HUVECs, ox-LDL induced significantly increased miR-2467-3p and decreased ABLIM1, and miR-2467-3p could negatively regulate ABLIM1. The knockdown of miR-2467-3p could alleviate the inhibited cell growth and motility by ox-LDL, and the inflammation and oxidative stress were also attenuated. While silencing could reverse the effect of miR-2467-3p on ox-LDL-induced HUVECs. The miR-2467-3p/ABLIM1 axis regulates the occurrence and development of DVT through modulating HUVECs inflammation and oxidative stress.

Free radical scavenging and anti-isolated human LDL oxidation activities of Butea superba Roxb. extract

BackgroundButea superba Roxb. (B. superba), is an herbal plant traditionally used for rejuvenation. Additionally, there have been reports on its antioxidant properties. Low-density lipoproteins (LDL) oxidation is the leading cause of cardiovascular diseases (CVDs). Natural products with antioxidant properties have the potential to inhibit LDL oxidation. However, no work has been done about the anti-isolated human LDL oxidation of B. superba extract (BSE). This study aimed to investigate the antioxidant potential of BSE and its ability to prevent isolated human (LDL) oxidation induced by free radical agents.MethodsThe antioxidant properties were investigated by antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS), ferric reducing ability power (FRAP), nitric oxide (NO) and peroxynitrite scavenging assay. More so, anti-isolated human LDL oxidation activities were evaluated by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) and 3-morpholinosydnonimine hydrochloride (SIN-1) induced LDL oxidation assay.ResultsBSE exhibited a significant (p < 0.05) antioxidant activity in all the test systems, demonstrating its potential as a potent free radical scavenger. It displayed scavenging effects on DPPH (p < 0.05; IC50 = 487.67 ± 21.94 µg/ml), ABTS (p < 0.05; IC50 = 30.83 ± 1.29 µg/ml). Furthermore, it generated significantly (p < 0.05) increased antioxidant capacity in a dose-dependent manner in FRAP assay and exhibited significantly (p < 0.01) higher percent NO scavenging activity than gallic acid. Besides, BSE at 62.5 µg/ml exhibited a considerable percent peroxynitrite scavenging of 71.40 ± 6.59% after a 2 h period. Moreover, BSE demonstrated anti-isolated human LDL oxidation activity induced by AAPH and SIN-1 (p < 0.05) and revealed scavenging activity similar to ascorbic acid (p > 0.05). Identifying the main constituents of BSE revealed the presence of genistein, daidzein, and biochanin A through Liquid Chromatography-Mass Spectrometer/Mass Spectrometer (LC–MS/MS) analysis.ConclusionThis is the first report that the presence of isoflavones in BSE could play an important role in its antioxidation and isolated human LDL oxidation scavenging properties. These findings suggest the potential for developing antioxidant herbal supplements. However, further studies must be investigated, including efficacious and safe human dosages.

Investigation of the effects of Terminalia chebula seed hydroalcoholic extract on Paraoxonase1 enzyme activity in rats

Background and aims: Paraoxonase 1 (PON1) is related to high-density lipoprotein (HDL) in serum and protects against low-density lipoprotein (LDL) oxidation. This study aimed to investigate the effects of Terminalia chebula on PON1 in hyperlipidemic rats and the molecular docking effects of some compounds of this medical plant on PON1 activity. Methods: Overall, 40 male rats (200–250 gr) were randomly divided into four groups, including the control group, the hyperlipid group, the hyperlipid group receiving 400 mg/kg of the hydroalcoholic extract of T. chebula seeds, and the hyperlipid group receiving 800 mg/kg of the hydroalcoholic extract of T. chebula seeds. The PON1 arylesterase activity in serum and the PON1 gene expression in the liver tissue underwent investigation. Then, the molecular docking effects of its compounds were studied on PON1 through in-silico studies using the AutoDock software (version 4.2.0). Results: T. chebula decreased (P&lt;0.001) the serum triglycerides from 105.88±10.15 mg/dL in the hyperlipidemic group to 66.88±14.90 and 74.25±9.51 mg/dL in hyperlipidemic groups receiving 400 and 800 mg/kg of the hydroalcoholic extract of T. chebula seeds, respectively. In addition, the PON1 serum aryl esterase activity increased from 202.12±6058 in hyperlipidemic rats to 224.34±58.74 (P=0.83) and 235.80±37.05 (P=0.6) in hyperlipidemic groups receiving 400 mg/kg and 800 mg/kg of the hydroalcoholic extract of T. chebula seeds, respectively. It also demonstrated a significant effect on PON1 gene expression (P&lt;0.001). In addition, the in-silico and docking results revealed that the main antioxidant compounds of T. chebula, such as catechin, kaempferol, and quercetin, could bind to the PON1 enzyme directly and influence the enzyme activity. Conclusion: T. chebula increased PON1 activity and PON1 gene expression. However, among the plant’s compounds, catechin, kaempferol, and quercetin played the most substantial role in the PON1 activity. It seems that these compounds can be useful as co-treatments in hyperlipidemia therapies.

Fatal attractions that trigger inflammation and drive atherosclerotic disease.

Atherosclerosis is the salient, underlying cause of cardiovascular diseases, such as arrhythmia, coronary artery disease, cardiomyopathy, pulmonary embolism and myocardial infarction. In recent years, atherosclerosis pathophysiology has evolved from a lipid-based to an inflammation-centric ideology. This narrative review is comprised of review and original articles that were found through the PubMed search engine. The following search terms or amalgamation of terms were used: "cardiovascular disease," "atherosclerosis," "inflammation," "GRP78," "Hsp60," "oxidative low-density lipoproteins," "aldehyde dehydrogenase," "β2-glycoprotein," "lipoprotein lipase A," "human cytomegalovirus." "SARS-CoV-2," "chlamydia pneumonia," "autophagy," "thrombosis" and "therapeutics." Emerging evidence supports the concept that atherosclerosis is associated with the interaction between cell surface expression of stress response chaperones, including GRP78 and Hsp60, and their respective autoantibodies. Moreover, various other autoantigens and their autoantibodies have displayed a compelling connection with the development of atherosclerosis, including oxidative low-density lipoproteins, aldehyde dehydrogenase, β2-glycoprotein and lipoprotein lipase A. Atherosclerosis progression is also concurrent with viral and bacterial activators of various diseases. This narrative review will focus on the contributions of human cytomegalovirus as well as SARS-CoV-2 and chlamydia pneumonia in atherosclerosis development. Notably, the interaction of an autoantigen with their respective autoantibodies or the presence of a foreign antigen can enhance inflammation development, which leads to atherosclerotic lesion progression. We will highlight and discuss the complex role of the interaction between autoantigens and autoantibodies, and the presence of foreign antigens in the development of atherosclerotic lesions in relationship to pro-inflammatory responses.

Synergistic Anti-Inflammatory Activity of Apolipoprotein A-I and CIGB-258 in Reconstituted High-Density Lipoproteins (rHDL) against Acute Toxicity of Carboxymethyllysine in Zebrafish and Its Embryo.

CIGB-258 is a 3 kDa altered peptide ligand from heat shock protein (HSP) 60 that exhibits anti-inflammatory activity against the acute toxicity of carboxymethyllysine (CML) with antioxidant and anti-glycation activities via protection of high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). It is necessary to test a synergistic interaction between apoA-I and CIGB-258 in reconstituted high-density lipoproteins (rHDL). Several rHDLs were synthesized containing palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apoA-I, and CIGB-258 at molar ratios of 95:5:1:0, 95:5:1:0.1, 95:5:1:0.5, and 95:5:1:1 for rHDL-(1:0), rHDL-(1:0.1), rHDL-(1:0.5), and rHDL-(1:1), respectively. As the CIGB-258 content in rHDL was increased, the particle size of rHDL was 1.4-times higher than rHDL-(1:0) to rHDL-(1:1), from 60 nm to 83 nm, respectively. As the CIGB-258 content was increased, the rHDL showed the most resistance to isothermal denaturation by a urea treatment, and rHDL-(1:1) exhibited the highest structural stability and the strongest antioxidant ability against LDL oxidation. Co-treatment of rHDL-(1:0), rHDL-(1:0.5), and rHDL-(1:1) resulted in up to 10%, 24%, and 34% inhibition of HDL glycation, inhibition of HDL glycation, which was caused by the CML, with protection of apoA-I. Microinjection of each rHDL into zebrafish embryos in the presence of CML showed that a higher CIGB-258 content in rHDL was associated with higher survivability with the least inflammation and apoptosis. Furthermore, an intraperitoneal injection of rHDL and CML showed that a higher CIGB-258 content in rHDL was also associated with higher survivability of zebrafish and faster recovery of swimming ability. The rHDL-(1:1) group showed the lowest triglyceride, AST, and ALT serum levels with the least production of interleukin-6, oxidized product, and neutrophil infiltration in hepatic tissue. In conclusion, CIGB-258 could bind well to phospholipids and cholesterol to stabilize apoA-I in the rHDL structure against denaturation stress and larger particle sizes. The rHDL containing CIGB-258 enhanced the in vitro antioxidant ability against LDL oxidation, the anti-glycation activity to protect HDL, and the in vivo anti-inflammatory activity against CML toxicity in zebrafish adults and embryos. Overall, incorporating apoA-I and CIGB-258 in rHDL resulted in a synergistic interaction to enhance the structural and functional correlations in a dose-dependent manner of CIGB-258.

Two Forms of C-Reactive Protein and Their Implication for Atherogenesis: Focus on Monomeric Form

In this review, we discuss the role of C-reactive protein (CRP), a biomarker of inflammation, in the development of atherosclerosis. CRP exists in two forms: the native pentameric form (nCRP) and the non-native form (mCRP), which is formed during inflammatory processes. The article explores the functions of both forms in atherosclerosis. nCRP binds to molecules with uncoated phosphocholine groups and activates the classical complement pathway. It can bind to enzymatically-modified LDL (E-LDL) and ox-LDL, affecting their pro-inflammatory properties and reducing LDL oxidation. nCRP also interacts with endothelial cells and reduces the absorption of acetylated LDL by these cells. In contrast, mCRP, formed in the presence of pathological conditions, exhibits distinct pro-inflammatory characteristics. While the role of nCRP in atherosclerosis remains unclear in animal models, mCRP has been associated with inflammation and is found in atherosclerotic lesions. The study suggests that nCRP may have atheroprotective effects, while mCRP may contribute to the progression of atherosclerosis. Further research is needed to fully understand the complex mechanisms of CRP in atherosclerosis.

Instant and short-term effects of acupuncture for depression and anxiety in unstable angina pectoris patients with percutaneous coronary interventions.

Patients with unstable angina pectoris (UAP) usually present anxiety or depression during percutaneous coronary intervention (PCI). This study sought to investigate the instant and short-term effects of acupuncture for anxiety and depression in UAP patients with PCI. A total of 210 UAP patients who underwent PCI were recruited and randomly assigned (1:1:1) to acupuncture, placebo, or control groups. Enzyme-linked immunosorbent assay was used to detect the levels of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), high-sensitivity C-reactive protein (Hs-CRP), advanced oxidation protein products (AoPPs), and oxidized low-density lipoprotein (OX-LDL). Serial questionnaires with the Hamilton Anxiety (HAMA) scale and the Pittsburgh Sleep Quality Index were evaluated, and heart rate variability indicators were obtained. Primary end-point: low frequency/high frequency (HF) was lower in the electroacupuncture group (p = 0.014), while standard deviation of normal-to-normal intervals, average standard deviation of normal-to-normal intervals, percentage of successive intervals that differ more than 50 ms, and HF were increased with acupuncture (p = 0.018, p = 0.043, p = 0.016, and p = 0.002, respectively). Secondary end-point: significant improvements in anxiety levels (HAMA) were observed in the three groups (p < 0.001). The fasting insulin and HOMA-IR levels were similar between the control group and the acupuncture group (p = 0.285 and p = 0.165, respectively). The levels of IL-6 and AoPPs differed among the three groups (p = 0.021 and p < 0.001, respectively). However, no significant differences were found in fasting plasma glucose, fasting c-peptide, Hs-CRP, and OX-LDL levels among the three groups (p = 0.585, p = 0.611, p = 0.902, and p = 0.756, respectively). In this study, short-term acupuncture may potentially relieve clinical symptoms before PCI treatment. ClinicalTrials.gov, identifier (NCT03789344).

Oxidative Changes among Women Suffering From Urinary Tract Infection in Enugu Metropolis, Nigeria

Background: The action of bacterial infection in the urinary tract can trigger the release of free radicals which could progress and overwhelm endogenous antioxidants, hence oxidative changes occur. This work aimed to estimate the level of oxidized low density lipoprotein (Ox-LDL) and superoxide dismutase (SOD), among women suffering from urinary tract infection in Enugu metropolis. Materials and Methods: Ethical approval was obtained from the Health Research and Ethics committee (HREC) of the University of Nigeria Teaching Hospital (UNTH), Ituku–Ozalla, Enugu State. Informed consent was obtained from all recruited subjects. About forty (40) women diagnosed of UTIs at the UNTH were recruited for the study and twenty (20) women free of UTIs and who are not registered with UNTH were used as a control for this study. Blood specimens were collected and analysed using the ELISA technique to check for Ox-LDL and SOD levels. Results: The mean value of the antioxidant enzyme, SOD, was lower than that of the control which suggests a possibility of oxidative stress. However, Ox-LDL mean value was lower than that of the control population showing absence of lipid peroxidation in all sampled population, which may have been pronounced if the subjects had complicated UTI like pyelonephritis. Conclusion: This study showed a drop in the levels of an antioxidant enzyme among UTI patients placing the patients at risk of oxidative stress. Ox-LDL should be higher in test than in control population indicating lipid peroxidation. However, in this study, the Ox-LDL showed no increase in values. Oxidative stress should be looked out for and treated by physicians when treating UTIs.

Investigation of fractions derived from the alcoholic extract of the Acacia root plant on LDL oxidation in vitro

Investigation of fractions derived from the alcoholic extract of the Acacia root plant on LDL oxidation in vitro

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure.

Cardiovascular disease is the cause of physical infirmity and thousands of deaths annually. Typically, during heart failure, cardiomyocyte mitochondria falter in terms of energy production and metabolic processing. Additionally, inflammation and the accumulation of non-contractile fibrous tissue contribute to cardiac malfunction. Melatonin, an endogenously produced molecule, experimentally reduces the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. The current review critically analyzes published data related to the experimental use of melatonin to forestall coronary artery pathologies. Collectively, these studies document melatonin's anti-atherosclerotic actions in reducing LDL oxidation and triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, preventing the proliferation and invasion of arterial smooth muscle cells into the lesioned area, restricting the ingrowth of blood vessels from the vasa vasorum, and solidifying the plaque cap to reduce the chance of its rupture. Diabetic hyperglycemia, which aggravates atherosclerotic plaque formation, is also inhibited by melatonin supplementation in experimental animals. The potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans should be seriously considered by performing clinical trials using this multifunctional molecule.

Effects of Herbs on Blood Pressure, Diabetes Mellitus, and Hyperlipidemia

Overweight and obesity in youth is a worldwide public health problem. Overweight and obesity in childhood and adolescents have a substantial effect upon many systems, resulting in clinical conditions such as metabolic syndrome, early atherosclerosis, dyslipidemia, hypertension and type 2 diabetes (T2D). Obesity and the type of body fat distribution are still the core aspects of insulin resistance and seem to be the physiopathologic links common to metabolic syndrome, cardiovascular disease and T2D. In presence of high levels of blood LDL particles, free radicals (ROS), macrophages, cytokines, platelets, histamine, 5HT get involved in LDL oxidation, leading to formation of atherosclerotic plaques which get deposited in endothelium of coronary arteries causing coronary artery disease (CAD). Psyllium fibers and Ficus Carica (FC) are being considered to be useful in treating hyperlipidemia, hypertension, and hyperglycemia. This study was conducted to determine hypotensive, hypolipidemic, and hypoglycemic potential of Psyllium husk and FC. Study was conducted in National hospital, Lahore, Pakistan from January to April 2019. Seventy five hyperlipidemic, hypertensive and diabetic patients were enrolled selected from the hospital with their consent. They were divided in three groups ie 25 patients in each group. Group-1 was on placebo, group-2 was on 15 grams psyllium husk to be used in three divided doses. Group-3 was on 12 grams FC to be taken in three divided doses daily for two months. Their Lipid profile, FBS, and hypertension were determined before and after two months therapy by these two agents. Two analyze data we used SPSS version 10.01.001 2015 and t test was applied to determine changes in the tested parameters. In two months therapy by psyllium husk in 24 patients TG, TC, LDL-c was reduced 21.48, 10.09, 24.17 mg/dl respectively. HDL was increased 12.38 mg/dl in this group. FBS reduction was 28.66 mg/dl, systolic BP 6.30, and diastolic BP reduced in this group 7.52 mm of mg. We then concluded that FC and PH have good enough potential to normalize lipid profile, reduce BP, and FBS in patients suffering from metabolic syndrome.

Gelatin-decorated Graphene oxide: A nanocarrier for delivering pH-responsive drug for improving therapeutic efficacy against atherosclerotic plaque

The progressive inflammatory disease atherosclerosis promotes myocardial infarction, stroke, and heart attack. Anti-inflammatory drugs treat severe atherosclerosis. They are inadequate bioavailability and cause adverse effects at higher doses. A new nanomaterial coupled pH-apperceptive drug delivery system for atherosclerotic plaque is outlined here. We have synthesized a Graphene Oxide-Gelatin-Atorvastatin (GO-Gel-ATR) nanodrug characterized by spectroscopic and imaging techniques. The encapsulation efficiency of GO-Gel-ATR (79.2%) in the loading process is observed to be better than GO-ATR (66.8%). The internal milieu of the plaque cells has a pH of 6.8. The GO-Gel-ATR displays sustained and cumulative release profile at pH 6.8 compared to ATR and GO-ATR. Our proposed nanocomposite demonstrated high cytocompatibility up to 100μg/mL in foam cells induced by Oxidized-Low Density Lipoprotein (Ox-LDL) and Lipopolysaccharides (LPS) compared to normal macrophages for 24 and 48 h. The uptake efficacy of the nanodrugs is shown to be enhanced in foam cells compared to normal macrophage. Oil red O staining of foam cells with and without drugs confirmed therapeutic efficacy. Foam cells treated with nanocomposite had more lipids efflux than ATR. The finding of the in-vitro study reveals that the GO-Gel-ATR nanocomposite carriers have the potential to deliver anti-atherosclerotic drugs effectively and inhibit atherosclerotic plaque progression.

Beeswax Alcohol Prevents Low-Density Lipoprotein Oxidation and Demonstrates Antioxidant Activities in Zebrafish Embryos and Human Subjects: A Clinical Study.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the effect of beeswax alcohol (BWA) was evaluated in the prevention of LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipid & protein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle-aged and older human subjects (n = 50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 μM), which was significantly better than the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails LDL/apo-B oxidation evoked by CuSO4 (final 0.5 μM) and a causes a marked reduction in lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 μM). Additionally, BWA counters the toxicity induced by carboxymethyllysine (CML, 500 ng) and rescues zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blinded, placebo-controlled preliminary clinical study on middle- and older-aged human subjects (n = 50) showed that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA) and total hydroperoxides and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo-control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in physical variables, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, in vitro, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and positively influences oxidative variables in human subjects.

Plasma/Serum Oxidant Parameters in Systemic Lupus Erythematosus Patients: A Systematic Review and Meta-Analysis.

Most published results have revealed variations in the association of serum/plasma levels of malondialdehyde (MDA), apolipoprotein B (ApoB), and oxidized low-density lipoprotein (OxLDL) and systemic lupus erythematosus (SLE). This study was performed to establish MDA, ApoB, and OxLDL levels in systemic lupus erythematosus (SLE) patients. Electronic databases were searched for the included articles up to 27th February 2023. The meta-analysis included 48 articles with 2358 SLE patients and 2126 healthy controls considered for MDA, ApoB, and OxLDL levels. There were significantly higher MDA, ApoB, and OxLDL levels in SLE patients than those in the control groups. Subgroup analysis indicated that European/American SLE patients and patients of both ages <36 and ≥36 exhibited higher MDA, ApoB, and OxLDL levels. Arab and Asian SLE patients had higher ApoB and MDA/OxLDL levels. African SLE patients recorded higher OxLDL levels than the control groups. SLE patients with a body mass index (BMI) of ≥23 and a disease duration of <10 recorded significantly higher MDA, ApoB, and OxLDL levels. Patients with systemic lupus erythematosus disease activity index (SLEDAI) ≥8 of SLE had higher MDA and ApoB levels, whereas SLE patients with SLEDAI <8 showed significantly higher ApoB levels. Patients with BMI <23 of SLE had higher MDA and OxLDL levels. This study established significantly higher MDA, ApoB, and OxLDL levels in SLE patients, suggesting a possible role of MDA, ApoB, and OxLDL in the disease.

Effect of Yoga-Based Cardiac Rehabilitation Program on Endothelial Function, Oxidative Stress, and Inflammatory Markers in Acute Myocardial Infarction: A Randomized Controlled Trial.

The aim of this study was to evaluate the effects of yoga-based cardiac rehabilitation (Yoga-CaRe) on the endothelial system, oxidative stress, and inflammatory markers in patients with acute myocardial infarction (MI). A sub-study was conducted in two clinical sites of the Yoga-CaRe trial (a multicenter randomized controlled trial). Participants with acute MI were randomized and allocated to either the Yoga-CaRe program (13 sessions with encouragement to home practice) or enhanced standard care (three educational sessions). Endothelial function, oxidative stress, and inflammatory biomarkers were assessed using biomarkers such as asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular cell-adhesion molecule-1, total nitric oxide concentration (NOx), oxidized low-density lipoprotein (Oxd-LDL), superoxide dismutase, total antioxidant capacity (TAOC), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) at baseline and 12 weeks. Laboratory and statistical analysis were done by staff blinded to group allocation. Eighty-two patients (of the 110 patients recruited) completed the study. The mean age was 53.1 ± 10.6 and 51.9 ± 10.7 years in enhanced standard care and Yoga-CaRe group, respectively. At 12 weeks, Yoga-CaRe significantly reduced ADMA, ET-1, and ICMA-1 than the enhanced standard care group. Although E-selectin and VCAM at 12 weeks were reduced in both groups, enhanced standard care had a significantly higher reduction than the Yoga-CaRe group. Among markers of oxidative stress, TAOC increased in the Yoga-CaRe group. We found no difference in eNOS, NOx, P-selectin, TNFα, CRP, and Oxd-LDL between the two groups. Yoga-CaRe improved the endothelial function (through a reduction in ET-1 and modulating adhesion molecules) and enhanced antioxidant capacity.

Relationships of apolipoprotein E genotypes with a cluster of seven in persons with type 2 diabetes.

The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes (2/2, 2/3, 2/4, 3/3, 3/4, and 4/4) for each member of the cluster of seven associated with type 2 diabetes (T2D). The cluster of seven includes abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDL-C) and increased plasma levels of triglycerides)), increased low-density lipoprotein (LDL) oxidation, and increased inflammation. Forty-six patients with well-controlled T2D participated in the study. Abdominal obesity (assessed by waist circumference), hypertension (measured by manual sphygmomanometry), platelet hyperaggregability (measured by bleeding time), hyperglycemia (by enzymatic kit and spectrophotometry), decreased plasma levels of HDL-C and increased plasma levels of triglycerides (by enzymatic kit and spectrophotometry), increased LDL oxidation (measured by LDL conjugated dienes using spectrophotometry) and increased inflammation measured by C-reactive protein (CRP) (by EIA kit) were determined. All genotypes, except 2/2 were found in the population studied. Abdominal obesity did not vary significantly across the five genotypes. However, glucose levels trended progressively higher going from 2/3 to 2/4 to 3/4 to 4/4. Systolic blood pressure was higher in 3/4 compared to 2/4 and trended higher in 3/4 compared to 3/3. Diastolic blood pressure trended higher in 3/3 vs 2/4 and significantly higher in 3/4 compared to 2/4. Triglycerides trended higher in 3/4 vs 3/3 while HDL-C came close to trending downward in 4/4 compared to 2/4. Bleeding time was unaffected by genotype. Plasma LDL conjugated dienes trended higher in 3/4 vs 2/4 and were significantly higher in 3/4 vs 3/3. CRP trended higher in 4/4 vs 2/3. We can conclude that those with at least one 4 allele in the presence of another allele being 2, 3 or 4 is potentially (in the case of trends) deleterious or is deleterious in terms of hyperglycemia, hypertension (systolic and diastolic blood pressure), dyslipidemia, LDL conjugated dienes and CRP levels.