LDL Oxidation Research Articles

Hesperidin Supplementation Improves Altered PON -1, LDL Oxidation, Inflammatory Response and Hepatic Function in an Experimental Rat Model of Hyperlipidemia.

In this study, we have examined the effect of hesperidin on rats fed on an experimental high-fat diet. Male Wistar rats were given a high-fat diet orally for one month for developing an HFD (High fat- diet) model. Rats were also supplemented with hesperidin (100mg/kg body weight) for one month. We determined serum LDL (Low-density lipoprotein) oxidation, Paraoxonase-1 (PON-1) activity, and histopathological profile of the liver. Inflammatory cytokines levels were also measured in serum. HFD induced significant changes in LDL oxidation and PON-1 activity. Liver tissue histopathology and gene expression of inflammatory markers (Il-6(Interleukin-6), TNF- alpha (Tumor necrosis factor alpha), NF-KB (Nuclear factor kappa B) show that significant changes occur in the hyperlipidemic model of rats. We also show that hesperidin can effectively improve plasma antioxidant, LDL oxidation, and inflammatory cytokine expression in rats already subjected to hyperlipidemic stress. We conclude that hesperidin may protect the liver from oxidative stress by improving hepatic function.

Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition on Podocytes in Mouse Nephrotic Syndrome

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known to play a crucial role in dyslipidemia, and an increase in serum PCSK9 levels has also been reported in patients with nephrotic syndrome (NS). However, the specific effects of PCSK9 in kidney disease and the therapeutic potential of targeting PCSK9 in NS remain elusive. We thus investigated the effects of evolocumab (EVO) in mice with adriamycin (ADR)-induced NS. Male BALB/c mice were divided into the following 4 groups: Control, N = 11; EVO (monoclonal antibody for PCSK9), N = 11; ADR, N = 11; and ADR+EVO, N = 11. We also performed in vitro experiments using immortalized murine podocyte cells to validate the direct effects of PCSK9 on podocytes. EVO decreased urinary albumin levels and ameliorated podocytopathy in mice with ADR nephropathy. Further, EVO suppressed the Nod-like receptor protein 3 (NLRP3) inflammasome pathway in podocytes. PCSK9 expression upregulated CD36, a scavenger receptor of oxidized low-density lipoprotein (Ox-LDL), which in turn stimulated the absorption of Ox-LDL in vitro. EVO downregulated CD36 expression in podocytes both in vitro and in vivo. Immunofluorescence staining analysis reveals that CD36 and PCSK9 colocalized in the glomerular tufts of mice with ADR nephropathy. In the patients with focal segmental glomerulosclerosis, the CD36+ area in glomerular tufts increased compared with those diagnosed with minor glomerular abnormalities. This study revealed that EVO ameliorated mouse ADR nephropathy through the regulation of CD36 and NLRP3 inflammasome signaling. EVO treatment represents a potential therapeutic strategy for human NS.

Binding properties of recombinant LDL receptor and LOX-1 receptor to LDL measured using bio-layer interferometry and atomic force microscopy

Oxidation of low-density lipoproteins (LDLs) triggers a recognition by scavenger receptors such as lectin-like oxidized LDL receptor-1 (LOX-1) and is related to inflammation and cardiovascular diseases. Although LDLs that are recognized by LOX-1 can be risk-related LDLs, conventional LDL detection methods using commercially available recombinant receptors remain undeveloped. Using a bio-layer interferometry (BLI), we investigated the binding of recombinant LOX-1 (reLOX-1) and LDL receptors to the oxidized LDLs. The recombinant LDL receptor preferably bound minimally modified LDLs, while the reLOX-1 recognized extensively oxidized LDLs. An inversed response of the BLI was observed during the binding in the case of reLOX-1. AFM study showed that the extensively oxidized LDLs and aggregates of LDLs were observed on the surface, supporting the results. Altogether, a combined use of these recombinant receptors and the BLI method is useful in detecting high-risk LDLs such as oxidized LDLs and modified LDLs.

CIRC_0091822 CONTRIBUTES TO THE PROLIFERATION, INVASION, AND MIGRATION OF VASCULAR SMOOTH MUSCLE CELLS UNDER OXIDIZED LOW-DENSITY LIPOPROTEIN TREATMENT.

Background: Circular RNAs (circRNAs) have been shown to mediate atherosclerosis (AS) process by regulating vascular smooth muscle cells (VSMCs) function. However, whether circ_0091822 mediates VSMCs function to regulate AS process is unclear. Methods: Oxidized low-density lipoprotein (ox-LDL) was used to treat VSMCs for constructing AS cell models. Vascular smooth muscle cells proliferation, invasion, and migration were examined by cell counting kit 8 assay, EdU assay, transwell assay, and wound healing assay. Protein expression was tested by western blot analysis. The expression of circ_0091822, microRNA (miR)-339-5p, and blocking of proliferation 1 (BOP1) was determined using quantitative real-time PCR. RNA interaction was examined using dual-luciferase reporter assay and RIP assay. Results: Ox-LDL treatment enhanced VSMCs proliferation, invasion, and migration. Circ_0091822 was overexpressed in the serum of AS patients and ox-LDL-induced VSMCs. Circ_0091822 knockdown inhibited ox-LDL-induced VSMCs proliferation, invasion, and migration. Circ_0091822 sponged miR-339-5p, and miR-339-5p inhibitor reversed the function of circ_0091822 knockdown. MiR-339-5p targeted BOP1, and BOP1 also reversed the repressing effect of miR-339-5p on ox-LDL-induced VSMCs functions. Circ_0091822/miR-339-5p/BOP1 axis promoted the activity of Wnt/β-catenin pathway. Conclusions: Circ_0091822 might be a therapeutic target for AS, which facilitated ox-LDL-induced VSMCs proliferation, invasion, and migration through modulating miR-339-5p/BOP1/Wnt/β-catenin pathway.

HDL Function and Atherosclerosis: Reactive Dicarbonyls as Promising Targets of Therapy.

Epidemiologic studies detected an inverse relationship between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major risk factor for ASCVD and suggesting atheroprotective functions of HDL. However, the role of HDL-C as a mediator of risk for ASCVD has been called into question by the failure of HDL-C-raising drugs to reduce cardiovascular events in clinical trials. Progress in understanding the heterogeneous nature of HDL particles in terms of their protein, lipid, and small RNA composition has contributed to the realization that HDL-C levels do not necessarily reflect HDL function. The most examined atheroprotective function of HDL is reverse cholesterol transport, whereby HDL removes cholesterol from plaque macrophage foam cells and delivers it to the liver for processing and excretion into bile. Indeed, in several studies, HDL has shown inverse associations between HDL cholesterol efflux capacity and ASCVD in humans. Inflammation plays a key role in the pathogenesis of atherosclerosis and vulnerable plaque formation, and a fundamental function of HDL is suppression of inflammatory signaling in macrophages and other cells. Oxidation is also a critical process to ASCVD in promoting atherogenic oxidative modifications of LDL (low-density lipoprotein) and cellular inflammation. HDL and its proteins including apoAI (apolipoprotein AI) and PON1 (paraoxonase 1) prevent cellular oxidative stress and LDL modifications. Importantly, HDL in humans with ASCVD is oxidatively modified rendering HDL dysfunctional and proinflammatory. Modification of HDL with reactive carbonyl species, such as malondialdehyde and isolevuglandins, dramatically impairs the antiatherogenic functions of HDL. Importantly, treatment of murine models of atherosclerosis with scavengers of reactive dicarbonyls improves HDL function and reduces systemic inflammation, atherosclerosis development, and features of plaque instability. Here, we discuss the HDL antiatherogenic functions in relation to oxidative modifications and the potential of reactive dicarbonyl scavengers as a therapeutic approach for ASCVD.

Cyclosporine A induces cardiac remodeling through TGF-β/Smad3/miR-29 signaling pathway and alters gene expression of miR-30b-5p/CaMKIIδ isoforms pathways: alleviating effects of moderate exercise.

Cyclosporine A (CsA)-induced cardiac interstitial fibrosis and cardiac hypertrophy are highly known phenomena; however, the basic mechanisms of CsA cardiotoxicity are unclear. The present study evaluated the role of the Transforming growth factor-beta (TGF-β)/Smad3/miR-29b signaling pathway and CaMKIIδ isoforms gene expression in cardiac remodeling under CsA exposure alone or combined with moderate exercise. A total of 24 male Wistar rats were divided into control, cyclosporine (30mg/kg BW), and cyclosporine-exercise groups. After 42 days of treatment, the findings revealed a significant decline in miR-29 and miR-30b-5p gene expression and an increase in gene expression of Smad3, calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) isoforms, Matrix Metalloproteinases (MMPs), protein expression of TGF-β, heart tissue protein carbonyl and oxidized LDL (Ox-LDL), and plasma LDL and cholesterol levels in the CsA-treated group compared to the control group. The CsA group presented greater histological heart changes such as fibrosis, necrosis, hemorrhage, infiltrated leukocyte, and left ventricular weight/heart weight than the control group. Moreover, combined moderate exercise and CsA relatively improved gene expression changes and histological alternations compared to the CsA group. TGF-β-Smad3-miR-29 and CaMKIIδ isoforms may mainly contribute to the progression of heart fibrosis and hypertrophy due to CsA exposure, providing new insight into the pathogenesis and treatment of CsA-induced side effects on the heart tissue.

ORal anticoaGulants in diAbetic and Nondiabetic patients with nOn-valvular atrial fibrillatioN (ORGANON)

BackgroundDiabetes represents a pro-thrombotic condition. ObjectivesThe primary objective was to evaluate the effects of Vitamin K Antagonist (VKA) compared to direct oral anticoagulants (DOACs) in diabetic and nondiabetic patients with non-valvular atrial fibrillation, newly diagnosed. The secondary objective was to evaluate the effects on the risk of bleeding. MethodsWe enrolled 300 patients with newly diagnosed atrial fibrillation. One hundred and sixteen patients were taking warfarin, 31 acenocumarol, 22 dabigatran, 80 rivaroxaban, 34 apixaban, and 17 edoxaban. We evaluated: anthropometric parameters, glycated hemoglobin (HbA1c), fasting and post-prandial glucose (FPG, and PPG), lipid profile, Lp(a), small and dense low-density lipoprotein (SD-LDL), oxidized LDL (Ox-LDL), I-troponin (I-Tn), creatinine, transaminases, iron, red blood cells (RBC); hemoglobin (Hb), platelets (PLT), fibrinogen, D-dimer, anti-thrombin III, C-reactive protein (Hs-CRP), Metalloproteinases-2 (MMP-2), Metalloproteinases-9 (MMP-9), and incidence of bleeding. ResultsWe did not record any differences among nondiabetic patients between VKA and DOACs. However, when we considered diabetic patients, we found a slight, but significant improvement of triglycerides and SD-LDL. As regards incidence of bleeding, minor bleeding was more frequent in VKA diabetic group compared to DOACs diabetic group; furthermore, the incidence of major bleeding was higher with VKA in nondiabetic and diabetic group, compared to patients with DOACs. Among DOACs, we recorded a higher incidence of bleeding (minor and major) with dabigatran compared to rivaroxaban, apixaban and edoxaban in nondiabetic and diabetic patients. ConclusionDOACs seem to be metabolically favourable in diabetic patients. Regarding incidence of bleeding, DOACs with the exception of dabigatran, seem better than VKA in diabetic patients.

MicroRNA-98 inhibition accelerates the development of atherosclerosis via regulation of dysfunction of endothelial cell

ABSTRACT Background Atherosclerosis has been recognized as a chronic inflammation initiated by dysfunction of endothelial cell that contributes to the increased morbidity and mortality of severe cardiovascular events. The reported important role of microRNA-98 (miR-98) in regulation of endothelial cell behaviors prompt us to hypothesize that miR-98 could be involved in the process of atherosclerosis. Methods and Results The current research showed the miR-98 expression was gradually down-regulated in atherosclerotic mouse arteries isolated from ApoE ablation mice subjected to high fat diet. Additionally, a dramatically reduced miR-98 expression in endothelial cells administrated to oxidized low-density lipoprotein (Ox-LDL) but a slight down-regulated level was found in macrophages. Functionally, attenuated miR-98 expression promoted secretion of chemokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs) induced by Ox-LDL, which subsequently increased infiltration and pro-inflammatory genes expression of macrophages, as well as the foam cell formation. Mechanistically, in vitro experiments indicated that the endothelial cell dysfunction regulated by miR-98 knockdown was partially contributed by upregulated expression of HMGB1. Furthermore, the animal experiment with ApoE−/− mice administrated with miR-98 inhibitor demonstrated that miR-98 silencing enhanced the atherosclerotic lesions in aorta and aortic sinus that were accompanied with increased adhesion molecules, chemokines, and pro-inflammatory markers expression. Conclusion MicroRNA-98 knockdown promoted endothelial cell dysfunction to affect the inflammatory state of macrophage and the development of atherosclerosis, at least partially, through direct targeting HMGB1. Collected, these data suggested that miR-98 could be a novel drug target for atherogenesis management.

Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2.

Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis. A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL). 415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)]. PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.

Cell-free hemoglobin-mediated oxidation of low-density lipoprotein (oxLDL) contributes to lung microvascular endothelial dysfunction during sepsis

Introduction: Disruption of the microvascular endothelial barrier is a critical pathological feature of sepsis-induced acute lung injury. Plasma cell-free hemoglobin (CFH) is elevated in approximately 80% of patients with sepsis and is independently associated with development of acute respiratory distress syndrome (ARDS) and mortality. Oxidized CFH (ferric, 3+) can oxidize low-density lipoprotein (oxLDL), which signals through its major endothelial receptor, the lectin-like oxidized LDL receptor 1 (LOX-1), to cause endothelial dysfunction through several pro-inflammatory pathways including activation of mitogen-activated protein kinases (MAPKs). However, little is known regarding whether LOX-1 receptor signaling leads to microvascular endothelial hyperpermeability or acute lung injury, especially in the context of sepsis. We hypothesized that oxidation of LDL by CFH contributes to lung microvascular endothelial barrier dysfunction and worse outcomes during sepsis through LOX-1 and downstream p38 MAPK. Methods: To test whether generation of oxLDL by CFH is associated with endothelial injury in clinical sepsis, circulating levels of CFH, oxLDL, and vascular injury marker sVE-cadherin were measured in 24 sepsis patients via ELISA and tested for association with development of ARDS. LDL was oxidized by combining LDL with CFH in a test tube overnight at 37°C and oxLDL was quantified by TBARS assay. In primary human lung microvascular endothelial cells (HLMVEC) transendothelial electrical resistance (TER), a measure of barrier dysfunction, was assessed by Electric Cell-substrate Impedance Sensing (ECIS). LOX-1 receptor was blocked using BI-0115 (Boehringer Ingelheim, 20 μM) and p38 MAPK was inhibited using NiPp (100 μM). Results: In sepsis patients, plasma oxLDL levels correlated with CFH (r=0.686, p=0.016) and sVE-cadherin (r=0.603, p=0.012), and tended to be higher in those who developed ARDS (38 U/L [IQR 27, 45] vs. 27 U/L [IQR 19, 35], p=0.1). Oxidation of LDL by CFH exacerbated HLMVEC barrier dysfunction compared to control, LDL, or CFH. Barrier dysfunction induced by CFH or oxLDL was attenuated by blocking the LOX-1 receptor or p38 MAPK. Conclusions: Increased plasma CFH and oxLDL are associated with vascular injury during clinical sepsis; one mechanism by which CFH may cause vascular hyperpermeability and sepsis-mediated lung injury is through oxidation of LDL which can drive signaling through the endothelial LOX-1 receptor and activation of p38 MAPK. NIH R35HL150783, R21GM144915, R01HL158906, R01HL164937, T32HL094296; Parker B. Francis Fellowship This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of almond intake on oxidative stress parameters: A systematic review and meta-analysis of clinical trials.

Several randomized controlled trials (RCTs) have shown that almonds can improve oxidative stress indices, but the results are controversial. Therefore, the goal of this research was to carry out a systematic review and meta-analysis of all RCTs that evaluated the effect of almonds on selected oxidative stress indices. A systematic search was conducted up to April 2022 on PubMed, Scopus, Web of Science, and Google Scholar. We have selected the studies that investigated the effects of almonds on malondialdehyde (MDA), and oxidized low-density lipoprotein (Ox-LDL) levels in adults. Data were pooled by using the random-effects model. The risk of bias in individual studies was assessed using the Cochrane Collaboration risk of bias tool. Seven RCTs involving 424 participants were analyzed. The results indicated that almond intake led to a significant decrease in MDA levels (WMD: -6.63nmol/ml; 95% CI: -8.72 to -4.54; P<0.001). However, no significant effect was observed on Ox-LDL (Hedges' g: -0.12; 95% CI: -0.34 to 0.10; P=0.28). Sensitivity analysis showed that overall estimates were not affected by the elimination of any study. We did not observe any evidence regarding publication bias. The present meta-analysis suggests that almond intake can improve MDA levels and might play a beneficial role in the reinforcement of the antioxidant defense system and amelioration of oxidative stress in adults. There is a need for more studies with larger groups to better estimate this effect.

Deletion of the scavenger receptor Scarb1 in myeloid cells does not affect bone mass.

The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a glycosylated cell surface receptor for high density lipoproteins (HDL), oxidized low density lipoproteins (OxLDL), and phosphocholine-containing oxidized phospholipids (PC-OxPLs). Scarb1 is expressed in macrophages and has been shown to have both pro- and anti-atherogenic properties. It has been reported that global deletion of Scarb1 in mice leads to either high or low bone mass and that PC-OxPLs decrease osteoblastogenesis and increase osteoclastogenesis. PC-OxPLs decrease bone mass in 6-month-old mice and are critical pathogenetic factors in the bone loss caused by high fat diet or aging. We have investigated here whether Scarb1 expression in myeloid cells affects bone mass and whether PC-OxPLs exert their anti-osteogenic effects via activation of Scarb1 in macrophages. To this end, we generated mice with deletion of Scarb1 in LysM-Cre expressing cells and found that lack of Scarb1 did not affect bone mass in vivo. These results indicate that Scarb1 expression in cells of the myeloid/osteoclast lineage does not contribute to bone homeostasis. Based on this evidence, and earlier studies of ours showing that Scarb1 expression in osteoblasts does not affect bone mass, we conclude that Scarb1 is not an important mediator of the adverse effects on PC-OxPLs in osteoclasts or osteoblasts in 6-month-old mice.

Ox-LDL aggravates contrast-induced injury of renal tubular epithelial cells.

Hypercholesterolemia can aggravate contrast-induced acute kidney injury, and the exacerbation of renal tubular epithelial cell (RTEC) injury is a major cause. However, the exact mechanisms remain obscure. Mitophagy, a type of autophagy, selectively eliminates damaged mitochondria and reduces mitochondrial oxidative stress, which is strongly implicated in cell homeostasis and acute kidney injury. Oxidized low-density lipoprotein (Ox-LDL) is accumulated in hypercholesterolemia and has a cytotoxic effect. This study aimed to determine whether and how ox-LDL exacerbates contrast-induced injury in RTECs and to further explore whether PINK1/Parkin-dependent mitophagy is involved in this process. Iohexol and ox-LDL were used alone or in combination to treat HK-2 cells. Rapamycin pretreatment was utilized to enhance mitophagy. Cell viability, apoptosis, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS) were detected by cell counting kit-8, TUNEL staining, JC-1 kit and MitoSOX fluorescence, respectively. The expression of mitophagy-related proteins (including PINK1, Parkin, and so on) and cleaved caspase-3 was confirmed by western blot. Colocalization of MitoTracker-labeled mitochondria and LysoTracker-labeled lysosomes was observed by fluorescence microscopy to evaluate mitophagy.The results of our study showed that ox-LDL aggravated MMP decline, mtROS release and apoptosis in iohexol-treated HK-2 cells, accompanied by a further increased autophagy level. Enhancement of PINK1/Parkin-dependent mitophagy by rapamycin alleviated apoptosis and mitochondrial injury in HK-2 cells in response to iohexol under ox-LDL condition.Therefore, our findings indicate that ox-LDL aggravates contrast-induced injury of RTECs by increasing mitochondrial damage and mitochondrial oxidative stress, which may be associated with the relative insufficiency of PINK1/Parkin-dependent mitophagy.

OA13 A study on subclinical atherosclerosis in Indian patients with psoriatic arthritis

Abstract Background/Aims Psoriatic Arthritis (PsA) is a type of chronic inflammatory arthritis with diverse extra-articular manifestations and complications, including an increased burden of cardiovascular (CV) disease. Traditional CV risk factors are more common in PsA patients, leading to not only overt but also subclinical CV disease. Endothelial dysfunction and altered handling of low-density lipoproteins (LDL) lead to atherogenesis. Oxidized LDL (Ox-LDL) and antibodies against it (Anti Ox-LDL) may reflect the in vivo inflammatory burden in systemic vasculature in PsA. This study aimed to assess subclinical atherosclerosis in PsA patients and compare them with healthy controls, by assessing carotid intimal medial thickness (CIMT) and laboratory surrogates of dyslipidemia. Methods This was a cross-sectional, case-control study. Between January 2019 and May 2020, adult patients classified as PsA as per the CASPAR criteria, with symptom duration of at least 2 years, were included in this study. An equal number of age- and gender-matched controls were enrolled. We excluded patients on lipid-lowering drugs for more than the past 3 months. Demographic details, clinical and laboratory parameters (including Ox-LDL and Anti Ox-LDL antibodies), and bilateral CIMT assessment using B-mode Doppler Ultrasonography by a single, blinded cardiologist, were assessed for each participant. The study was approved by the Institutional Ethics Committee. Results Fifty PsA patients consented to the study, with a median age of 43.92 ± 10.79 years. Fifty healthy controls were also enrolled. 57% of the cases were male, with plaque psoriasis in 94%, and polyarthritis in 54%. Compared to the controls, PsA patients had significantly higher mean body mass index (BMI, 26.5 vs 24.6, p = 0.004), mean VLDL (25.6 mg/dl vs 20.5 mg/dl, p = 0.01), mean bilateral CIMT (0.62 mm vs 0.46 mm, p &amp;lt; 0.001), and mean Anti Ox-LDL antibody levels (29 U/ml vs 22.4 U/ml, p &amp;lt; 0.001). There was a significantly greater proportion of PsA patients with total cholesterol to HDL ratio &amp;gt;3.5 (86% vs 68%, p = 0.03), obesity (18% vs 6%, p = 0.01), and Anti Ox-LDL &amp;gt;30 U/ml (32% vs 6%, p = 0.02). CIMT and Anti Ox-LDL levels did not show any significant correlation. Univariate and multivariate analyses revealed that older patient age, total cholesterol level, and presence of PsA were risk factors for increased mean CIMT as a proxy for subclinical atherosclerosis. Conclusion This study used a novel biomarker, the Anti-Ox-LDL antibody, as a proposed surrogate marker for atherosclerotic risk stratification in patients with PsA. To our knowledge, this is the first such study in PsA. We found an increased prevalence of subclinical atherosclerosis in PsA patients compared to age- and gender-matched healthy controls. Age, total cholesterol levels, and the presence of PsA were independent predictors of atherosclerotic risk. Anti-Ox-LDL antibodies are significantly elevated in PsA patients compared to controls, but they may not correlate well with CIMT values. Disclosure D. Yadavalli: None. S. Ghosh: None. S. Dhuria: None. K. Telang: None. L. Sharma: None. R. Bajaj: None. V. Singal: None. R. Gupta: None.

A Systematic Review of the Effects of Smoking on the Cardiovascular System and General Health.

The main risk factor for atherosclerotic cardiovascular disease is smoking. Nicotine and carbon monoxide are two dangerous substances that are found in cigarette smoke. The increased heart rate can have an almost instantaneous impact on the heart and blood vessels. Smoking is well known to cause oxidative stress, endanger the lining of the arteries, and accelerate the accumulation of fatty plaque in the blood vessels. It raises the danger of sudden thrombotic events, inflammatory alterations, and low-density lipoprotein oxidation. The smoke's carbon monoxide decreases the blood's capacity to deliver oxygen, adding to the heart's stress. Notably, these risks increase when diabetes, hypertension, high cholesterol, and glucose intolerance are present. It has a detrimental effect on peripheral blood vessels, raising the possibility of thromboangiitis obliterans. Stroke risk is known to be increased by smoking. As compared to those who continue to smoke, those who give up smoking have a much longer life expectancy. Chronic cigarette smoking has been shown to affect the macrophages' ability to remove cholesterol. Abstinence from smoking enhances the function of high-density lipoproteins and cholesterol efflux, lowering the risk of plaque buildup. In this review, we present the most recent information regarding the causal relationship between smoking and cardiovascular health as well as the long-term advantages of quitting.

Effects of oleoylethanolamide supplementation on inflammatory biomarkers, oxidative stress and antioxidant parameters of obese patients with NAFLD on a calorie-restricted diet: A randomized controlled trial.

Background: Oxidative stress is considered a major factor in the pathophysiology of non-alcoholic liver disease (NAFLD). A growing body of evidence indicates that oleoylethanolamide (OEA), a bioactive lipid mediator, has anti-inflammatory and antioxidant properties. This trial investigated the effects of OEA administration on inflammatory markers, oxidative stress and antioxidant parameters of patients with NAFLD. Methods: The present randomized controlled trial was conducted on 60 obese patients with NAFLD. The patients were treated with OEA (250mg/day) or placebo along with a low-calorie diet for 12 weeks. Inflammatory markers and oxidative stress and antioxidant parameters were evaluated pre-and post-intervention. Results: At the end of the study, neither the between-group changes, nor the within-group differences were significant for serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1 beta (IL-1β), IL-6, IL-10, and tumor necrosis-factor α (TNF-α). Serum levels of total antioxidant capacity (TAC) and superoxide dismutase (SOD) significantly increased and serum concentrations of malondialdehyde (MDA) and oxidized-low density lipoprotein (ox-LDL) significantly decreased in the OEA group compared to placebo at study endpoint (p = 0.039, 0.018, 0.003 and 0.001, respectively). Although, no significant between-group alterations were found in glutathione peroxidase and catalase. There were significant correlations between percent of changes in serum oxidative stress and antioxidant parameters with percent of changes in some anthropometric indices in the intervention group. Conclusion: OEA supplementation could improve some oxidative stress/antioxidant biomarkers without any significant effect on inflammation in NAFLD patients. Further clinical trials with longer follow-up periods are demanded to verify profitable effects of OEA in these patients. Clinical Trial Registration: www.irct.ir, Iranian Registry of Clinical Trials IRCT20090609002017N32.

Dysfunctional antioxidant capacity of high-density lipoprotein in rheumatoid arthritis.

High-density lipoprotein (HDL) presents atheroprotective functions not readily reflected by plasma HDL-cholesterol levels. The aim of this study was to investigate HDL antioxidant function in patients with rheumatoid arthritis (RA). This pilot and cross-sectional study included 50 RA patients and 50 controls matched by age, gender, cardiovascular risk factors and drug therapy. The antioxidant capacity of HDL was assessed by the total radical-trapping antioxidative potential test (TRAP-assay) and the susceptibility of low-density lipoprotein (LDL) to oxidation by the Conjugated Dienes Assay (Dmax ). A carotid ultrasound was performed in all participants to detect subclinical atherosclerosis. High-density lipoprotein from RA patients showed lower antioxidant capacity than those from controls [oxidized-LDL%: 35.8 (27-42) vs. 24.4 (20-32), p < .001] when analysed with the TRAP-assay. In addition, the time to achieve 50% of maximal LDL oxidation (Lag-time) was shorter in RA-patients than in matched controls [57.2 (42-71) vs. 69.5 (55-75) minutes, (p = .003)]. RA patients showed a higher atherosclerotic burden than controls. The pro-oxidant pattern in RA was irrespective of the presence of carotid atherosclerosis. On the contrary, there was a positive correlation between inflammatory parameters (erythrocyte sedimentation rate, ultrasensitive C-reactive protein and fibrinogen) and the loss of HDL-anti-oxidant capacity measured by the TRAP-assay (rho = .211, p = .035; rho = .231, p = .021 and rho = .206, p = .041, respectively). Furthermore, the glucocorticoid dose at recruitment was negatively associated with the Lag-time in RA patients (rho = -.387, p = .026). Rheumatoid arthritis patients present reduced HDL antioxidant capacity and a lower resistance of LDL particles to oxidation, mainly related to the degree of inflammation.

Inhibition of lncRNA NFIA-AS1 Alleviates Abnormal Proliferation and Inflammation of Vascular Smooth Muscle Cells in Atherosclerosis by Regulating miR-125a-3p/AKT1 Axis.

Vascular smooth muscle cells (VSMCs) are critical elements of the vascular wall and play a crucial role in the genesis and development of atherosclerosis (AS). Increasingly, studies have indicated that long noncoding RNAs (lncRNAs) regulate VSMC proliferation, apoptosis, and other biological processes. Nevertheless, the role of lncRNA NFIA-AS1 (hereinafter referred to as NFIA-AS1) in VSMCs and AS remains unclear. Quantitative real-time PCR (qRT-PCR) was performed to analyze the messenger RNA (mRNA) levels of NFIA-AS1 and miR-125a-3p. CCK-8 and EdU staining were performed to detect VSMC proliferation. VSMC apoptosis was evaluated by flow cytometry. The expression of various proteins was detected using western blotting. The levels of inflammatory cytokines secreted by VSMCs were measured by enzyme linked immunosorbent assay (ELISA). The binding sites of NFIA-AS1 and miR-125a-3p, as well as miR-125a-3p and AKT1, were analyzed using bioinformatics methods and validated using a luciferase reporter assay. The function of NFIA-AS1/miR-125a-3p/AKT1 in VSMCs was clarified through loss- and gain-of-functional experiments. We confirmed that NFIA-AS1 was highly expressed in AS tissues and VSMCs induced by oxidized low-density lipoprotein (Ox-LDL). Knockdown of NFIA-AS1 restrained the exceptional growth of Ox-LDL-induced VSMCs, promoted their apoptosis, and decreased the secretion of inflammatory factors and expression of adhesion factors. In addition, NFIA-AS1 regulated the proliferation, apoptosis, and inflammatory response of VSMCs through the miR-125a-3p/AKT1 axis, suggesting that NFIA-AS1 may be a potential therapeutic target for AS.

Dry Fruits: Contain Chemicals to Keep Human Body Organs Healthy

Hyperglycemia, hypertension, and hyperlipidemia are known as metabolic syndrome. 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 2020. 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.

Potential Biomarkers and Therapeutic Targets: Inflammation and Oxidative Stress in Left Carotid Artery Stenosis with Coronary Artery Disease.

Patients with left carotid artery atherosclerotic stenosis have an increased ischemic stroke risk. Left carotid stenosis, the most common cause of the transient ischemic attack, is related to a higher risk of acute stroke. Left carotid artery stenosis is also associated with cerebral artery infarction. The significant coronary stenosis promotes ST-segment elevation myocardial infarctions. The severe coronary stenosis plays an important role in development and progression of myocardial infarction. However, the dynamic changes of circulating oxidative stress and inflammatory markers in the carotid stenosis combined with coronary artery stenosis are not clear, and it also remains unknown whether markers of oxidative stress and inflammation are potential therapeutic targets for carotid stenosis combined with coronary artery stenosis. This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients. We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2-isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients. Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients. Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.