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Methods in Molecular Biology (Clifton,... 2022Lipid particles found in circulating extracellular fluids such as blood or lymph are essential for cellular homeostasis, metabolism and survival. Such particles provide...
Lipid particles found in circulating extracellular fluids such as blood or lymph are essential for cellular homeostasis, metabolism and survival. Such particles provide essential lipids and fats which enable cells to synthesize new membranes and regulate different biochemical pathways. Imbalance in lipid particle metabolism can cause pathological states such as atherosclerosis. Here, elevated low-density lipoprotein (LDL) accumulation leads to fat-filled lesions or plaques in arterial walls. In this chapter, we provide a detailed set of protocols for the rapid and safe purification of lipid particles from human blood using high-speed ultracentrifugation. We provide a detailed set of assays for further analysis of the biochemical and cellular properties of these lipid particles. By combining these assays, we can better understand the complex roles of different lipid particles in normal physiology and disease pathology.
Topics: Atherosclerosis; Humans; Lipid Metabolism; Lipoproteins, LDL; Ultracentrifugation
PubMed: 35237966
DOI: 10.1007/978-1-0716-1924-7_12 -
Analytica Chimica Acta Jun 2020Oxidized-low-density lipoprotein (oxLDL) is well-recognized as an actual patho-atherogenic lipoprotein: elevated serum concentration of oxLDL increases the risk for...
Oxidized-low-density lipoprotein (oxLDL) is well-recognized as an actual patho-atherogenic lipoprotein: elevated serum concentration of oxLDL increases the risk for developing atherosclerosis, leading to coronary artery disease (CAD). Herein, we report an approach for sensing oxLDL directly in serum with molecularly imprinted polymer (MIP) thin films on quartz crystal microbalance (QCM). The resulting MIP sensors show low cross-reaction toward low-density lipoprotein (LDL) and high-density lipoprotein (HDL): signals are around one magnitude smaller. Very-low-density lipoprotein (VLDL) and human serum albumin (HSA) do not lead to any significant sensor response. The sensor allowed for accurately assessing oxLDL over the detection range of 86-5600 μg dL, which covers the clinically relevant concentrations. The sensor determines oxLDL with recovery accuracy of 92-107% and a precision of 1-8% coefficient variation. Compared with commercially available oxLDL ELISA test kit our sensor reveals similar characteristics obtaining a correlation coefficient of 0.98. However, the sensors have rapid response times of 10 min compared to 210 min of ELISA, which demonstrates their efficiency in assessing this sensitive atherogenic biomarker for CAD diagnostics.
Topics: Biomimetics; Humans; Lipoproteins, LDL; Molecular Imprinting; Molecularly Imprinted Polymers; Polymethacrylic Acids; Povidone; Quartz Crystal Microbalance Techniques
PubMed: 32389186
DOI: 10.1016/j.aca.2020.04.017 -
Molecules (Basel, Switzerland) Feb 2023Low-density lipoproteins (LDLs) exert a key role in the transport of esterified cholesterol to tissues. Among the atherogenic modifications of LDLs, the oxidative...
Low-density lipoproteins (LDLs) exert a key role in the transport of esterified cholesterol to tissues. Among the atherogenic modifications of LDLs, the oxidative modification has been mainly investigated as a major risk factor for accelerating atherogenesis. Since LDL sphingolipids are also emerging as important regulators of the atherogenic process, increasing attention is devoted to the effects of sphingomyelinase (SMase) on LDL structural and atherogenic properties. The aims of the study were to investigate the effect of SMase treatment on the physical-chemical properties of LDLs. Moreover, we evaluated cell viability, apoptosis, and oxidative and inflammatory status in human umbilical vein endothelial cells (HUVECs) treated with either ox-LDLs or SMase-treated LDLs (SMase-LDLs). Both treatments were associated with the accrual of the intracellular ROS and upregulation of the antioxidant Paraoxonase 2 (PON2), while only SMase-LDLs induced an increase of superoxide dismutase 2 (SOD2), suggesting the activation of a feedback loop to restrain the detrimental effects of ROS. The increased caspase-3 activity and reduced viability observed in cells treated with SMase-LDLs and ox-LDLs suggest a pro-apoptotic effect of these modified lipoproteins on endothelial cells. Moreover, a strong proinflammatory effect of SMase-LDLs compared to ox-LDLs was confirmed by an increased activation of NF-κB and consequent increased expression of its downstream cytokines IL-8 and IL-6 in HUVECs.
Topics: Humans; Human Umbilical Vein Endothelial Cells; Sphingomyelin Phosphodiesterase; Reactive Oxygen Species; Lipoproteins, LDL; Antioxidants; Apoptosis; Atherosclerosis; Oxidative Stress
PubMed: 36903354
DOI: 10.3390/molecules28052100 -
International Journal of Molecular... Jul 2022The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of... (Review)
Review
The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of phosphatidylcholine by phospholipase A2 (PLA2) and is catabolized to other substances by different enzymatic pathways. LPC exerts pleiotropic effects mediated by its receptors, G protein-coupled signaling receptors, Toll-like receptors, and ion channels to activate several second messengers. Lysophosphatidylcholine (LPC) is increasingly considered a key marker/factor positively in pathological states, especially inflammation and atherosclerosis development. Current studies have indicated that the injury of nervous tissues promotes oxidative stress and lipid peroxidation, as well as excessive accumulation of LPC, enhancing the membrane hyperexcitability to induce chronic pain, which may be recognized as one of the hallmarks of chronic pain. However, findings from lipidomic studies of LPC have been lacking in the context of chronic pain. In this review, we focus in some detail on LPC sources, biochemical pathways, and the signal-transduction system. Moreover, we outline the detection methods of LPC for accurate analysis of each individual LPC species and reveal the pathophysiological implication of LPC in chronic pain, which makes it an interesting target for biomarkers and the development of medicine regarding chronic pain.
Topics: Atherosclerosis; Chronic Pain; Humans; Lipoproteins, LDL; Lysophosphatidylcholines; Phospholipases A2; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 35955410
DOI: 10.3390/ijms23158274 -
Biochemical and Biophysical Research... Jun 2021Helicobacter pylori (H. pylori) infection mainly causes gastroduodenal diseases, including chronic gastritis, peptic ulcer disease and gastric cancer. In recent years,...
Helicobacter pylori (H. pylori) infection mainly causes gastroduodenal diseases, including chronic gastritis, peptic ulcer disease and gastric cancer. In recent years, several studies have demonstrated that infection with H. pylori, especially strains harboring the virulence factor CagA (cytotoxin-associated gene A), contribute to the development of non-gastric systemic diseases, including hypercholesterolemia and atherosclerotic cardiovascular diseases. However, mechanisms underlying this association has not been defined. In this study, we carried out a large-scale genetic screen using Drosophila and identified a novel CagA target low-density lipoprotein receptor (LDLR), which aids in the clearance of circulating LDL. We showed that CagA physically interacted with LDLR via its carboxy-terminal region and inhibited LDLR-mediated LDL uptake into cells. Since deficiency of LDLR-mediated LDL uptake has been known to increase plasma LDL and accelerate atherosclerosis, our findings may provide a novel mechanism for the association between infection with CagA-positive H. pylori and hypercholesterolemia leading to atherosclerotic cardiovascular diseases.
Topics: Animals; Animals, Genetically Modified; Antigens, Bacterial; Atherosclerosis; Bacterial Proteins; Drosophila melanogaster; Eye; Female; Helicobacter pylori; Humans; Hypercholesterolemia; Lipoproteins, LDL; Male; Protein Binding; Receptors, LDL; Virulence Factors
PubMed: 33845309
DOI: 10.1016/j.bbrc.2021.03.170 -
Archives of Razi Institute Oct 2022Smoking destroys the vascular system, increases plaque deposits in atherosclerosis, and increases inflammation. The present study was performed to determine the effect...
Smoking destroys the vascular system, increases plaque deposits in atherosclerosis, and increases inflammation. The present study was performed to determine the effect of smoking on the levels of low-density lipoprotein and very low-density lipoprotein in smokers. A cross-control study was carried out in the outpatient clinic in Baghdad, Iraq. The study was carried out 60 by individuals from February 2021 to July 2021. Participants in this study included adult smokers and non-smokers of both genders, and the levels of LDL and VLDL were determined using an Automatic Chemistry Analyze. The results revealed that the total number of smokers was 60 individuals from both genders; there was a significant difference in mean low-density lipoprotein and very low-density lipoprotein levels. There is a significant difference in LDL Values between non-smokers and smokers (129.853±7.880; <0.05). Non-smokers showed lower LDL values (104.460±7.950; <0.05). Regarding VLDL values, results revealed that smokers were showing higher values than a non-smoker (49.641±4.02), (28.986±1.676) respectively, <0.05). LDL and VLDL levels are more prevalent in current cigarette smokers than in non-smokers. Heavy smokers have higher LDL and VLDL values for a cigarette than non-smokers, which is consistent with observations in other populations.
Topics: Female; Humans; Male; Iraq; Lipoproteins, LDL; Smokers; Smoking; Adult
PubMed: 37123165
DOI: 10.22092/ARI.2022.358326.2191 -
Molecular Biology Reports Mar 2022The production of lipid-laden cells in macrophages after significant ingestion of oxidized low-density lipoprotein is considered the most critical phase in the creation... (Review)
Review
BACKGROUND
The production of lipid-laden cells in macrophages after significant ingestion of oxidized low-density lipoprotein is considered the most critical phase in the creation of atherosclerotic lesions, which is known as foam cell formation. Targeting foam cell development to find a potential therapeutic strategy for the management of atherosclerosis has yielded numerous promising outcomes. Multiple variables influence foam cell growth, including scavenger receptor expression, cholesterol transporter expression acyl CoA: cholesterol acyltransferase activity, and neutral cholesteryl ester hydrolase activity. Plants used during herbal therapy have been shown to assist with a variety of ailments.
RESULT
In this study, we found medicinal plants and their bioactive components suppress foam cell formation in a variety of ways; some inhibit cholesterol transporter and lectin-like oxidized low-density lipoprotein receptor-1 upregulation, while others inhibit the function of acyl CoA: cholesterol acyltransferase activity, and neutral cholesteryl ester hydrolase activity.
CONCLUSION
Recent study findings related to the synthesis of the new active component from plant sources by focusing on the typical process involved in the generation of foam cells. We're also looking at using a cellular target-based therapeutic approach to generate novel plant-based medications for the cure of atherosclerosis.
Topics: Atherosclerosis; Cholesterol; Foam Cells; Gene Expression; Humans; Lipoproteins, LDL; Macrophages
PubMed: 35013861
DOI: 10.1007/s11033-021-07039-9 -
Journal of the American College of... Jan 2023
Topics: Humans; Cholesterol, LDL; Dietary Supplements; Hypercholesterolemia; Cholesterol, Dietary; Lipoproteins, LDL; Cholesterol, HDL
PubMed: 36599607
DOI: 10.1016/j.jacc.2022.11.004 -
Advances in Food and Nutrition Research 2020This chapter reports essential information about the protective action of antioxidants against LDL oxidation. The activity of individual compounds (tocopherols, vitamin... (Review)
Review
This chapter reports essential information about the protective action of antioxidants against LDL oxidation. The activity of individual compounds (tocopherols, vitamin C, phenolic compounds) as well as extracts obtained from plant material (cereals, fruits, legumes, nuts, mushrooms, by-products of food industry) is reported. The structure-antioxidant activity relationship of phenolic compounds is discussed. This article summarizes the findings to date of both in vitro and in vivo studies using foods or phenolic extracts isolated from foodstuffs at inhibiting the incidence of LDL oxidation. This chapter summarizes also the reportings to date of in vivo studies using foods or beverages at inhibiting the incidence of LDL oxidation.
Topics: Animals; Antioxidants; Ascorbic Acid; Biological Products; Diet; Female; Humans; Lipoproteins, LDL; Male; Oxidation-Reduction; Phenols; Plant Extracts; Plants, Edible; Tocopherols
PubMed: 32711864
DOI: 10.1016/bs.afnr.2020.04.002 -
Blood Advances Apr 2023Low-density lipoprotein (LDL) contributes to atherogenesis and cardiovascular disease through interactions with peripheral blood cells, especially platelets. However,...
Low-density lipoprotein (LDL) contributes to atherogenesis and cardiovascular disease through interactions with peripheral blood cells, especially platelets. However, mechanisms by which LDL affects platelet activation and atherothrombosis, and how to best therapeutically target and safely prevent such responses remain unclear. Here, we investigate how oxidized low-density lipoprotein (oxLDL) enhances glycoprotein VI (GPVI)-mediated platelet hemostatic and procoagulant responses, and how traditional and emerging antiplatelet therapies affect oxLDL-enhanced platelet procoagulant activity ex vivo. Human platelets were treated with oxLDL and the GPVI-specific agonist, crosslinked collagen-related peptide, and assayed for hemostatic and procoagulant responses in the presence of inhibitors of purinergic receptors (P2YR), cyclooxygenase (COX), and tyrosine kinases. Ex vivo, oxLDL enhanced GPVI-mediated platelet dense granule secretion, α-granule secretion, integrin activation, thromboxane generation and aggregation, as well as procoagulant phosphatidylserine exposure and fibrin generation. Studies of washed human platelets, as well as platelets from mouse and nonhuman primate models of hyperlipidemia, further determined that P2YR antagonists (eg, ticagrelor) and Bruton tyrosine kinase inhibitors (eg, ibrutinib) reduced oxLDL-mediated platelet responses and procoagulant activity, whereas COX inhibitors (eg, aspirin) had no significant effect. Together, our results demonstrate that oxLDL enhances GPVI-mediated platelet procoagulant activity in a manner that may be more effectively reduced by P2YR antagonists and tyrosine kinase inhibitors compared with COX inhibitors.
Topics: Humans; Mice; Animals; Platelet Aggregation Inhibitors; Tyrosine Kinase Inhibitors; Lipoproteins, LDL; Hemostatics
PubMed: 36219587
DOI: 10.1182/bloodadvances.2022007169