LDL Oxidation Research Articles

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.

Effect of Drying Method and Coating With Gum Arabic on Physicochemical Properties, Betalain Content, LDL Oxidation, and Storage Stability of Dried Red Beetroot Slices

Effect of Drying Method and Coating With Gum Arabic on Physicochemical Properties, Betalain Content, LDL Oxidation, and Storage Stability of Dried Red Beetroot Slices

Influence of Abdominal Obesity on the Relationship of Low-Density Lipoprotein Cholesterol with Atherosclerosis and Cardiovascular Risk in Rheumatoid Arthritis

Methods. Coronary artery calcium, number of coronary plaques, and extensive ( 5 plaques) or obstructive (&gt;50% stenosis) disease was evaluated with computed tomography angiography in 150 patients at baseline and 101 patients 6.9±0.4 years later. Cardiovascular events were recorded. Oxidized LDL was measured with monoclonal antibody E06. Serum cholesterol loading capacity on macrophages was measured as intracellular cholesterol content with a fluorometric assay. Results. Abdominal obesity was not associated with per-patient number of coronary plaques or coronary artery calcium score at baseline. Low LDLc positively associated with number of plaques (b 2.13 [95% confidence interval 1.03 to 3.22]), likelihood of extensive or obstructive plaque (odds ratio 6.58, 95% confidence interval [1.63 to 26.46]), and log-transformed CAC (b 1.90 [0.89 to 2.91]) exclusively in nonobese patients (p-for-interaction &lt;0.001, 0.061, and 0.001 respectively). Low LDLc associated with increased likelihood of &gt;median oxidized LDL and higher ratio of cholesterol loading capacity to LDLc in nonobese patients (p-for-interaction 0.041 and 0.001 respectively). Abdominal obesity negatively associated with likelihood of plaque stenosis progression (odds ratio 0.19 [0.07 to 0.54]). Low LDLc associated with greater likelihood of per-segment plaque formation (OR 4.68 [2.26 to 9.66]) and increased stenotic severity (odds ratio 5.35 [1.62 to 17.67]) only in nonobese patients (p-for-interaction 0.002 and 0.040 respectively). Abdominal obesity was not linked to cardiovascular risk (Hazard Ratio 1.57, 95% confidence interval [0.66-3.73]). Low LDLc associated with higher cardiovascular risk in nonobese (Hazard Ratio 7.94 [1.52 to 41.36]) but not obese patients (p-for-interaction=0.017). Conclusion. Abdominal obesity was not linked to plaque progression or cardiovascular risk in RA. Only in nonobese patients, low LDLc associated with higher atherosclerosis burden, plaque progression and cardiovascular risk. This may reflect higher oxidation and macrophage cholesterol loading capacity of LDL when LDLc is &lt;70mg/dl.

Role of High-sensitivity C-reactive Protein in Future Cardiovascular Events in Hemodialysis Patients.

The pathogenesis of cardio-vascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX-3) and the oxidative stress-related biomarker soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX-1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30; 95%CI=1.20-4.43). In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.

Bioactive Flavonoids in Protecting Against Endothelial Dysfunction and Atherosclerosis.

Atherosclerosis is a common cardiovascular disease closely associated with factors such as hyperlipidaemia and chronic inflammation. Among them, endothelial dysfunction serves as a major predisposing factor. Vascular endothelial dysfunction is manifested by impaired endothelium-dependent vasodilation, enhanced oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, endothelial senescence, and endothelial-mesenchymal transition (EndoMT). Flavonoids are known for their antioxidant activity, eliminating oxidative stress induced by reactive oxygen species (ROS), thereby preventing the oxidation of low-density lipoprotein (LDL) cholesterol, reducing platelet aggregation, alleviating ischemic damage, and improving vascular function. Flavonoids have also been shown to possess anti-inflammatory activity and to protect the cardiovascular system. This review focuses on the protective effects of these naturally-occuring bioactive flavonoids against the initiation and progression of atherosclerosis through their effects on endothelial cells including, but not limited to, their antioxidant, anti-inflammatory, anti-thrombotic, and lipid-lowering properties. However, more clinical evidences are still needed to determine the exact role and optimal dosage of these compounds in the treatment of atherosclerosis.

OxLDL-Stimulated Macrophages Transmit Exosomal MicroRNA-320b to Aggravate Viability, Invasion, and Phenotype Switching via Regulating PPARGC1A-Mediated MEK/ERK Pathway in Proatherogenic Vascular Smooth Muscle Cells.

Our previous study revealed oxidized-low density lipoprotein (oxLDL)-stimulated macrophages delivered exosomes to exacerbate vascular smooth muscle cell (VSMC) viability and invasion; and microRNA-320b was enriched in exosomes from oxLDL-stimulated macrophages. This study aimed to further explore molecular mechanisms of exosomal microRNA-320b from oxLDL-stimulated macrophages on cellular functions of VSMCs. Exosomes from oxLDL-stimulated macrophages with microRNA-320b mimic/inhibitor transfection were used to treat VSMCs. Next, microRNA-320b mimic/inhibitor, and microRNA-320b mimic with or without peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) overexpression vector were transfected into VSMCs. Viability, invasion, apoptosis, contractile/synthetic phenotype markers, and MEK/ERK pathway were detected in VSMCs. Exosomes from microRNA-320b mimic-treated macrophages promoted viability, invasion, and synthetic phenotype marker osteopontin, while suppressed apoptosis and contractile phenotype marker α-smooth muscle actin in VSMCs. Importantly, direct microRNA-320b mimic treatment aggravated viability, invasion, and synthetic phenotype transition in VSMCs. However, microRNA-320b inhibitor showed the opposite effects as microRNA-320b mimic. Next, luciferase reporter gene assay showed that microRNA-320b directly bound to PPARGC1A; microRNA-320b also inversely regulated PPARGC1A in VSMCs. Moreover, the effect of microRNA-320b mimic on cellular functions of VSMCs was hampered by PPARGC1A overexpression vector (all P < 0.05). Additionally, microRNA-320b activated MEK/ERKT pathway, which was also suppressed by PPARGC1A overexpression vector (all P < 0.05). OxLDL-stimulated macrophages deliver exosomal microRNA-320b to exacerbate viability, invasion, and synthetic phenotype transition in VSMCs via modulating PPARGC1A-mediated MEK/ERK pathway, thus participating in the progression of atherosclerosis.

Olive Oil's Attenuating Effects on Lipotoxicity.

Dietary fatty acids play a role in the pathogenesis of obesity-associated nonalcoholic fatty liver disease. Lipotoxicity in obesity mediates insulin resistance, endothelial dysfunction, atherosclerosis, and gut microbiota dysbiosis. Cardiovascular complications are the main cause of morbidity and mortality in obese, insulin-resistant, and type 2 diabetes mellitus patients.Interventions targeting lipotoxicity are the main issue in preventing its multiple insults. Lifestyle modifications including healthy eating and regular exercise are the primary recommendations. Treatments also include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation, fibrogenesis, and cirrhosis.Diet and nutrition have been linked to insulin resistance, an increased risk of developing type 2 diabetes, and impaired postprandial lipid metabolism. Low-fat diets are associated with higher survival. The Mediterranean diet includes an abundance of olive oil. Extra-virgin olive oil is the main source of monounsaturated fatty acids in Mediterranean diets. An olive oil-rich diet decreases triglyceride accumulation in the liver, improves postprandial triglyceride levels, improves glucose and insulin secretions, and upregulates GLUT-2 expression in the liver. The exact molecular mechanisms of olive oil's effects are unknown, but decreasing NF-kB activation, decreasing LDL oxidation, and improving insulin resistance by reducing the production of inflammatory cytokines (TNF-α and IL-6) and upregulating kinases and JNK-mediated phosphorylation of IRS-1 are possible principal mechanisms. Olive oil phenolic compounds also modulate gut microbiota diversity, which also affects lipotoxicity.In this review, we document lipotoxicity in obesity manifestations and the beneficial health effects of the Mediterranean diet derived from monounsaturated fatty acids, mainly from olive oil.

Central Role of β-1,4-GalT-V in Cancer Signaling, Inflammation, and Other Disease-Centric Pathways.

UDP-Galactose: Glucosylceramide, β-1,4-Galactose transferase-V (β-1,4-GalT-V), is a member of a large glycosyltransferase family, primarily involved in the transfer of sugar residues from nucleotide sugars, such as galactose, glucose mannose, etc., to sugar constituents of glycosphingolipids and glycoproteins. For example, UDP-Galactose: Glucosylceramide, β-1,4-galactosyltransferase (β-1,4-GalT-V), transfers galactose to glucosylceramide to generate Lactosylceramide (LacCer), a bioactive "lipid second messenger" that can activate nicotinamide adenine dinucleotide phosphate(NADPH) oxidase (NOX-1) to produce superoxide's (O2-) to activate several signaling pathways critical in regulating multiple phenotypes implicated in health and diseases. LacCer can also activate cytosolic phospholipase A-2 to produce eicosanoids and prostaglandins to induce inflammatory pathways. However, the lack of regulation of β-1,4-GalT-V contributes to critical phenotypes central to cancer and cardiovascular diseases, e.g., cell proliferation, migration, angiogenesis, phagocytosis, and apoptosis. Additionally, inflammation that accompanies β-1,4-GalT-V dysregulation accelerates the initiation and progression of cancer, cardiovascular diseases, as well as inflammation-centric diseases, like lupus erythematosus, chronic obstructive pulmonary disease (COPD), and inflammatory bowel diseases. An exciting development in this field of research arrived due to the recognition that the activation of β-1,4-GalT-V is a "pivotal" point of convergence for multiple signaling pathways initiated by physiologically relevant molecules, e.g., growth factors, oxidized-low density lipoprotein(ox- LDL), pro-inflammatory molecules, oxidative and sheer stress, diet, and cigarette smoking. Thus, dysregulation of these pathways may well contribute to cancer, heart disease, skin diseases, and several inflammation-centric diseases in experimental animal models of human diseases and in humans. These observations have been described under post-transcriptional modifications of β-1,4- GalT-V. On the other hand, we also point to the important role of β-1-4 GalT-V-mediated glycosylation in altering the formation of glycosylated precursor forms of proteins and their activation, e.g., β-1 integrin, wingless-related integration site (Wnt)/-β catenin, Frizzled-1, and Notch1. Such alterations in glycosylation may influence cell differentiation, angiogenesis, diminished basement membrane architecture, tissue remodeling, infiltrative growth, and metastasis in human colorectal cancers and breast cancer stem cells. We also discuss Online Mendelian Inheritance in Man (OMIM), which is a comprehensive database of human genes and genetic disorders used to provide information on the genetic basis of inherited diseases and traits and information about the molecular pathways and biological processes that underlie human physiology. We describe cancer genes interacting with the β-1,4-GalT-V gene and homologs generated by OMIM. In sum, we propose that β-1,4-GalT-V gene/protein serves as a "gateway" regulating several signal transduction pathways in oxidative stress and inflammation leading to cancer and other diseases, thus rationalizing further studies to better understand the genetic regulation and interaction of β-1,4-GalT-V with other genes. Novel therapies will hinge on biochemical analysis and characterization of β-1,4-GalT-V in patient-derived materials and animal models. And using β-1,4-GalT-V as a "bonafide drug target" to mitigate these diseases.

Metabolites of Rusuvastatin Inhibit Oxidation of both Low-Density Lipoproteins and Very Low-Density Lipoproteins

Coronary Artery Disease is caused by plaque buildup in the walls of the arteries that supply blood to the heart (called coronary arteries) and other parts of the body. Plaque is made up of deposits of cholesterol and other substances in the artery. Plaque buildup causes the inside of the arteries to narrow over time, which could partially or totally block the blood flow. This process is called atherosclerosis. Coronary artery disease (CAD), when get worst, it is known as coronary artery syndrome (CAS). There are many allopathic medications which can stop, even at starting points of the disease (CAD). Hypolipidemic drugs like statins, fibrates, resins and niacin are well known agents used for prevention of CAD. There are ethnic-based medicinal herbs which can be used to treat or prevent CAD with narrow to moderate range of statistical significance. We compared Rosuvastatin 10 mg with Indian dates (Jujubes) as hypolipidemic agents. This research was conducted at Ghurki Trust Teaching Hospital, jalo park, Lahore, Pakistan. Duration of study was two months. Twenty to seventy years old 60 hyperlipidemic patients of both gender were included in research work with written consent. We divided these patients in two equal groups. Group-I was advised to take Tablet Rosuvastatin 10 mg, twice daily for two months. Group-II was advised to take 500 grams Indian dates for two months. Their baseline parameters like LDL-cholesterol, HDL-cholesterol, systolic/diastolic blood pressure was determined in the hospital laboratory. Separate file was maintained for their name, age, sex, occupation, and address. After two months therapy we compiled data related to tested parameters. Paired t-test was applied to compare changes in all parameters. Their mean values with ± SD before and after treatment were compared and analyzed statistically. It was observed that Rosuvastatin significantly decreased systolic/diastolic blood pressure, LDL-cholesterol, and increased HDL-cholesterol in 27 hyperlipidemic/hypertensive patients. Indian dates used in 30 hyperlipidemic patients significantly decreased systolic blood pressure, and LDL-cholesterol, but insignificant changes were seen in diastolic blood pressure, and HDL-cholesterol. We concluded from the research work that Rosuvastatin is potent hypolipidemic and hypotensive medicine as compared to indian dates.

Enhancement of Antioxidant and Anti-Glycation Properties of Beeswax Alcohol in Reconstituted High-Density Lipoprotein: Safeguarding against Carboxymethyllysine Toxicity in Zebrafish.

The antioxidant and anti-inflammatory abilities of beeswax alcohol (BWA) are well reported in animal and human clinical studies, with a significant decrease in malondialdehyde (MDA) in the blood, reduced liver steatosis, and decreased insulin. However, there has been insufficient information to explain BWAs in vitro antioxidant and anti-inflammatory activity owing to its limited solubility in an aqueous buffer system. Herein, three distinct reconstituted high-density lipoproteins (rHDL) were prepared with palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apolipoprotein A-I (apoA-I), and BWA at molar ratios of 95:5:1:0 (rHDL-0), 95:5:1:0.5 (rHDL-0.5), and 95:5:1:1 (rHDL-1) and examined for antioxidant and anti-glycation effects. A rHDL containing BWA, precisely rHDL-1, displayed a remarkable anti-glycation effect against fructose (final 250 mM), induced glycation of HDL, and prevented proteolytic degradation of apoA-I. Also, BWA incorporated rHDL-0.5, and rHDL-1 displayed substantial antioxidant activity by inhibiting cupric ion-mediated low-density lipoprotein (LDL) oxidation. In contrast to rHDL-0, a 20 and 22% enhancement in ferric ion reduction ability (FRA) and paraoxonase (PON) activity was observed in HDL treated with rHDL-1, signifying the effect of BWA on the antioxidant activity enhancement of HDL. rHDL-1 efficiently inhibits Nε-carboxylmethyllysine (CML)-induced reactive oxygen species (ROS) generation and apoptosis in zebrafish embryos, consequently improving embryo survivability and developmental deformities impaired by the CML. The dermal application of rHDL-1 to the CML-impaired cutaneous wound of the adult zebrafish inhibited ROS production and displayed potent wound-healing activity. Conclusively, incorporating BWA in rHDL significantly enhanced the anti-glycation and antioxidant activities in rHDL via more stabilization of apoA-I with a larger particle size. The rHDL containing BWA facilitated the inherent antioxidant ability of HDL to suppress the CML-induced toxicities in zebrafish embryos and ameliorate CML-aggravated chronic wounds in adult zebrafish.

LncRNA MIR4697HG Alleviates Endothelial Cell Injury and Atherosclerosis Progression in Mice via the FUS/ANXA5 Axis.

Atherosclerosis (AS) manifests with arterial intimal injury, lipid deposition and chronic inflammation, which is a key pathogenic cause of cardio-cerebrovascular disorders. LncRNA MIR4697HG was downregulated in human advanced atherosclerotic plaques. This study probed the precise biological functions and downstream regulatory mechanisms of MIR4697HG during AS progression. MIR4697HG levels in atherosclerotic plaque tissues and normal arterial intima were measured by RT-qPCR. An injury model of human umbilical vein endothelial cells (HUVECs) was induced through treating with oxidative low-density lipoprotein (ox-LDL). MIR4697HG overexpression plasmids (pcDNA-MIR4697HG) was transfected into ox-LDL-treated HUVECs, and then cell viability, apoptosis, reactive oxygen species (ROS) level, oxidative stress marker protein malondialdehyde (MDA) level and superoxide dismutase (SOD) activity, and adhesion molecule intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels in HUVECs were determined. Moreover, the binding between MIR4697HG and fused in sarcoma (FUS) was checked with RNA pull-down assay. The interaction between FUS and annexin A5 (ANXA5) was gauged with Co-immunoprecipitation. Then MIR4697HG/FUS/ANXA5 axis mediated HUVEC functions were accessed with rescue experiments. Additionally, an AS model was established via feeding a high-fat diet for ApoE-/- mice, and lentivirus MIR4697HG overexpression vector (Lv-MIR4697HG) was injected into AS mice followed by detection of atherosclerotic plaque area in mice. MIR4697HG was downregulated in atherosclerotic plaque tissues and HUVECs stimulated by ox-LDL. MIR4697HG overexpression attenuated ox-LDL-induced HUVEC viability inhibition, apoptosis, oxidative stress and adhesion molecule release. Moreover, MIR4697HG bound with FUS and facilitated FUS expression in HUVECs. FUS knockdown abrogated the functions of lncRNA MIR4697HG overexpression in ox-LDL induced HUVEC injury. Besides, FUS could bind with ANXA5. FUS overexpression inhibited ox-LDL induced HUVEC injury, while ANXA5 knockdown reversed these effects. Additionally, Lv-MIR4697HG reduced atherosclerotic plaque area in ApoE-/- mice. LncRNA MIR4697HG mitigated ox-LDL-induced apoptosis, oxidative stress and adhesion molecule release in HUVECs and alleviated AS progression in mice through the FUS/ANXA5 axis.

Exploiting the beneficial effects of Salvia officinalis L. extracts in human health and assessing their activity as potent functional regulators of food microbiota

Salvia officinalis L. has attracted scientific and industrial interest due to its pharmacological properties. However, its detailed phytochemical profile and its correlation with beneficial effects in the human microbiome and oxidative stress remained elusive. To unveil this, S. officinalis was collected from the region of Epirus and its molecular identity was verified with DNA barcoding. Phytochemical profile for both aqueous and ethanol-based extracts was determined by high-pressure liquid chromatography-tandem mass spectrometry and 103 phytochemicals were determined. The effect of S. officinalis extracts as functional regulators of food microbiota by stimulating the growth of Lacticaseibacillus rhamnosus strains and by suppressing evolution of pathogenic bacteria was verified. Furthermore, we recorded that both extracts exhibited a significant cellular protection against H2O2-induced DNA damage. Finally, both extracts exhibited strong inhibitory effect towards LDL oxidation. This study provides a comprehensive characterization of S. officinalis on its phytochemical components as also its potential impact in human microbiome and oxidative stress.

Effect of alkyl‐chain unsaturation on the antioxidant potential of chlorogenic acid derivatives in food and biological systems

SummaryChlorogenic acid (CGA) was modified using acyl chlorides with different levels of unsaturation (C18:0–C18:3) to enhance the lipophilicity and promote its application. The antioxidant activity of CGA derivatives in food and biological models was evaluated. All CGA derivatives had significantly greater antioxidative activity than CGA in fish oil and β‐carotene/linoleic acid emulsions (P &lt; 0.05), but there was no linear relationship between antioxidative activity and unsaturation. The effectiveness of CGA‐C18:0 was significantly greater than that of CGA in scavenging H2O2 and reducing copper‐induced human low‐density lipoprotein (LDL) oxidation (P &lt; 0.05). Furthermore, the H2O2 scavenging activity, inhibitions of copper‐induced human LDL oxidation and hydroxyl or peroxyl radical‐induced DNA oxidation were all linearly related to the unsaturation of the alkyl chains, mainly with the free radical chain reactions of the unsaturated bonds. Our findings showed that CGA derivatives could potentially be used as antioxidants in food and biological systems.

Increased 12/15-lipoxygenase by disturbed flow promotes endothelial dysfunction and the development of atherosclerosis

Abstract Introduction Atherosclerosis is predisposed at bifurcations, branch points and arterial curvatures where the blood flow is disturbed. Deposition and oxidative modification of low-density lipoprotein (LDL) in the subendothelial intima is an early event in the pathogenesis of atherosclerosis. However, the effect of disturbed flow (d-flow) on LDL oxidation and the underlying mechanisms remain unclear. Purpose In this study, we investigated the role of 12/15-lipoxygenase (LOX) in LDL oxidation in endothelial cells (EC) and the development of atherosclerosis at d-flow sites. Methods En face immunofluorescence was performed to analyze the expression of 12/15-LOX in EC under exposure to different flow patterns. Protein expression and LDL oxidation was studied in vitro by using 2 different flow apparatuses. Animal model of d-flow was established by partial ligation of the carotid artery. Results En face staining exhibited a significant increase in 12/15-LOX protein expression in EC in areas exposed to d-flow than those exposed to steady flow (s-flow). Carotid partial ligation in ApoE knockout mice led to substantially increased deposition of oxidized LDL in the subendothelial intima and formation of atherosclerotic plaques in the carotid artery, whereas these detrimental effects by d-flow were markedly attenuated in ApoE/12/15-LOX double knockout mice. In cultured EC, d-flow generated by a reversal flow pump markedly promoted the expression of 12/15-LOX and translocation of the protein onto the cell membrane. Inhibition of 12/15-LOX in EC, either by knockdown with its specific siRNA or a pharmacological inhibitor, suppressed production of 15s-HETE and LDL oxidation in response to d-flow. Mechanically, we found d-flow induced the expression of 12/15-LOX by activating a specific responsive element in the 12/15-LOX promoter through recruiting a shear stress-sensitive transcriptional factor SREBP2. Chromatin immunoprecipitation further confirmed the interaction of SREBP2 with the promoter of 12/15-LOX upon d-flow exposure. Conclusions These data define an essential role of 12/15-LOX in promoting the pathogenesis of atherosclerosis under d-flow by increasing LDL oxidation in EC through SREBP2 signaling.

Abstract 16934: Eicosapentaenoic Acid Inhibits Lipoprotein(a) With Higher Rates of Oxidation Compared to Non-Modified Low-Density Lipoprotein in vitro

Background: Lp(a) synthesis is the result of covalent binding of apolipoprotein a to apolipoprotein B on LDL particles. Elevated Lp(a) levels are an independent and causal risk factor for cardiovascular (CV) disease. Atherogenic mechanisms for Lp(a) include increased inflammation due to its associated oxidized lipids. The omega-3 fatty acid (n3-FA) EPA administered as icosapent ethyl reduced CV events in REDUCE-IT. As a potential mechanism, EPA inhibits oxidation of different sized ApoB-containing lipoproteins compared to other n3-FAs. We tested EPA effects on oxidation of lipoprotein samples enriched with Lp(a) compared to control LDL samples. Methods: Lp(a) was enriched to 40% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) (100 μg/mL) and non-modified LDL were incubated at 37°C for 30 min with EPA (50 μM). Samples were then subjected to copper sulfate-induced oxidation (20 μM) monitored by formation of malondialdehyde (MDA). Results: Lp(a) enriched ApoB particles underwent increased oxidation by 18% after 2 h which was significantly higher than non-modified LDL (13.24 ± 0.47 vs 11.23 ± 0.44 μM, p&lt;0.001). EPA significantly inhibited Lp(a) and non-modified LDL oxidation; after 2 h, EPA inhibited MDA levels by 56% and 76%, respectively (p&lt;0.001). The inhibition of oxidation in both particles with EPA was time dependent. Conclusions: Lp(a) enriched plasma underwent oxidation to a greater extent than non-modified LDL and this process was inhibited in a dose-dependent fashion by EPA. The antioxidant actions of EPA may contribute to reduced events in outcome trials, including in subjects with elevated Lp(a).

An Overview of Dietary Flavonoids as a Nutraceutical Nanoformulation Approach to Life-Threatening Diseases.

Obesity, heart disease, diabetes, and cancer are just a few chronic diseases for which proper nutrition has been demonstrated to be a crucial factor in preven-tion. Flavonoids, found in many fruits and vegetables, are a type of dietary polyphenol with potent antioxidant activity and anti-carcinogenic characteris-tics. Flavonoids and foods rich in flavonoids have been shown in recent years to have profound effects on cognitive function, aging, and neurodegenerative diseases like Alzheimer's. Foods high in flavonoids, such as green tea, choco-late, blueberries, and other fruits and vegetables, have ameliorated symptoms of cognitive impairment, Alzheimer's disease, and dementia in several animal models. As a result of their ability to prevent neuronal death generated by neu-rotoxic chemicals such as free radicals and β-amyloid proteins. Furthermore, flavonoids are also effective in slowing the evolution of clinical signs of neuro-degenerative illnesses. In addition, flavonoids can improve lipid profiles by preventing the oxidation of low-density lipoproteins, and these antioxidant ca-pabilities are responsible for their therapeutic impacts. Finally, the potential of flavonoids to induce vasodilation and control apoptotic processes in the endo-thelium is another way in which they benefit the cardiovascular system. This review aims to offer up-to-date information on categorizing these compounds, their primary methods of action in the human body, and their positive impacts on the management of neurodegenerative diseases, cardiovascular disorders, and other life-threatening diseases.

Quercetin and Heart Health: From Molecular Pathways to Clinical Findings

Cardiovascular diseases (CVD) are the leading causes of global death, increasing over time. Despite current novel improvements, it is still a major medical challenge. Quercetin (QU) is a flavonoid with anti-inflammatory, vasodilatory, antihypertensive, antiarrhythmogenic, and antiapoptotic effects. It can reduce low-density lipoprotein (LDL) and cholesterol oxidation and prevent endothelial dysfunction in CVD. Also, it can protect myocardial cells against oxidative stress and inflammation caused by free radicals. An updated review of the literature on the cardiovascular effects of quercetin was performed using PubMed, Embase, and Science Direct databases. The aim of this review is to summarize the various effects of quercetin on the cardiovascular system.

Simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) by probe-type ultrasound-assisted natural deep eutectic solvents and their inhibition effects on low density lipoprotein oxidation

The simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) was performed by integrating natural deep eutectic solvents (NADES) and ultrasound-assisted extraction (UAE). Among the eight kinds of NADES screened, choline chloride-1,2-propylene glycol was the most suitable extractant. The probe-type ultrasound-assisted NADES extraction system (pr-UAE-NADES) demonstrated higher extraction efficiency compared with plate-type ultrasound-assisted NADES extraction system (pl-UAE-NADES). Orthogonal experimental design and a modified multi-index synthetic weighted scoring method were adopted to optimize pr-UAE-NADES extraction process. The optimal extraction conditions that had a maximum synthetic weighted score of 29.46 were determined to be 25 °C for extraction temperature, 600 W for ultrasonic power, 20 min for extraction time, and 25% (w/w) for water content in NADES, leading to the maximum yields (7.39 ± 0.20 mg/g and 57.99 ± 0.91 mg/g, respectively) of crocin and geniposide. Thirty-three compounds including iridoids, carotenoids, phenolic acids, flavonoids, and triterpenes in the NADES extract were identified by LC-Q-TOF-MS2 coupled with a feature-based molecular networking workflow. The kinetics evaluation of the conjugated dienes generation on Cu2+-induced low density lipoprotein (LDL) oxidation via the four-parameter logistic regression model showed that crocin increased the lag time of LDL oxidation in a concentration-dependent manner (15 μg/mL, 30 μg/mL, 45 μg/mL) by 12.66%, 35.44%, and 73.42%, respectively. The quantitative determination for fluorescence properties alteration of the apolipoprotein B-100 exhibited that crocin effectively inhibited the fluorescence quenching of tryptophan residues and the modification of lysine residues caused by reactive aldehydes and malondialdehydes. The pr-UAE-NADES showed significant efficiency toward the simultaneous extraction of crocin and geniposide from gardenia fruits. And this study demonstrates the potential utility of gardenia fruits in developing anti-atherogenic functional food.