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Biosensors Jun 2021The excess of low-density lipoprotein (LDL) strongly promotes the accumulation of cholesterol on the arterial wall, which can easily lead to the atherosclerotic...
The excess of low-density lipoprotein (LDL) strongly promotes the accumulation of cholesterol on the arterial wall, which can easily lead to the atherosclerotic cardiovascular diseases (ACDs). It is a challenge on how to recognize and quantify the LDL with a simple and sensitive analytical technology. Herein, β-cyclodextrins (β-CDs), acting as molecular receptors, can bind with LDL to form stable inclusion complexes via the multiple interactions, including electrostatic, van der Waals forces, hydrogen bonding and hydrophobic interactions. With the combination of gold nanoparticles (Au NPs) and β-CDs, we developed an electrochemical sensor providing an excellent molecular recognition and sensing performance towards LDL detection. The LDL dynamic adsorption behavior on the surface of the β-CD-Au electrode was explored by electrochemical impedance spectroscopy (EIS), displaying that the electron-transfer resistance (Ret) values were proportional to the LDL (positively charged apolipoprotein B-100) concentrations. The β-CD-Au modified sensor exhibited a high selectivity and sensitivity (978 kΩ·µM) toward LDL, especially in ultra-low concentrations compared with the common interferers HDL and HSA. Due to its excellent molecular recognition performance, β-CD-Au can be used as a sensing material to monitor LDL in human blood for preventing ACDs in the future.
Topics: Adsorption; Biosensing Techniques; Electrochemical Techniques; Electrodes; Gold; Humans; Lipoproteins, LDL; Metal Nanoparticles; beta-Cyclodextrins
PubMed: 34209334
DOI: 10.3390/bios11070216 -
International Journal of Molecular... Apr 2023Ovarian aging hampers in vitro fertilization in assisted reproductive medicine and has no cure. Lipoprotein metabolism is associated with ovarian aging. It remains...
Ovarian aging hampers in vitro fertilization in assisted reproductive medicine and has no cure. Lipoprotein metabolism is associated with ovarian aging. It remains unclear how to overcome poor follicular development with aging. Upregulation of the low-density lipoprotein receptor (LDLR) enhances oogenesis and follicular development in mouse ovaries. This study investigated whether upregulation of LDLR expression using lovastatin enhances ovarian activity in mice. We performed superovulation using a hormone and used lovastatin to upregulate LDLR. We histologically analyzed the functional activity of lovastatin-treated ovaries and investigated gene and protein expression of follicular development markers, using RT-qPCR and Western blotting. Histological analysis showed that lovastatin significantly increased the numbers of antral follicles and ovulated oocytes per ovary. The in vitro maturation rate was 10% higher for lovastatin-treated ovaries than for control ovaries. Relative LDLR expression was 40% higher in lovastatin-treated ovaries than in control ovaries. Lovastatin significantly increased steroidogenesis in ovaries and promoted the expression of follicular development marker genes such as anti-Mullerian hormone, Oct3/4, Nanog, and Sox2. In conclusion, lovastatin enhanced ovarian activity throughout follicular development. Therefore, we suggest that upregulation of LDLR may help to improve follicular development in clinical settings. Modulation of lipoprotein metabolism can be used with assisted reproductive technologies to overcome ovarian aging.
Topics: Female; Animals; Mice; Ovary; Lovastatin; Ovarian Follicle; Oocytes; Lipoproteins, LDL; Lipoproteins
PubMed: 37108426
DOI: 10.3390/ijms24087263 -
Prostaglandins & Other Lipid Mediators Oct 2019Oxidized-low-density lipoprotein (ox-LDL), as well as high-density lipoprotein (HDL) and its subfractions play important role in the development of coronary artery...
BACKGROUND
Oxidized-low-density lipoprotein (ox-LDL), as well as high-density lipoprotein (HDL) and its subfractions play important role in the development of coronary artery disease (CAD).
METHODS
A total of 1417 individuals who received selective coronary angiography (CAG) without lipids-lowering treatments were consecutively enrolled. Patients were divided into CAD (n = 942) and non-CAD group (n = 475). The severity of CAD was assessed by Gensini Scores (GS) system. The correlations of ox-LDL with HDL subfractions were analyzed.
RESULTS
Compared with non-CAD subjects, CAD patients had higher ox-LDL but lower concentrations of HDL cholesterol (p = 0.002) and large HDL subfractions (p = 0.004). And ox-LDL was negatively correlated with large HDL subfractions in patients with severe CAD (p < 0.05). Moreover, ox-LDL was elevated and large HDL subfractions decreased with the increase of the number of stenotic coronary arteries and GS (p < 0.05, respectivelly).
CONCLUSIONS
The correlations between ox-LDL and cholesterol level of large HDL particles varied among CAD and non-CAD, and CAD with different severities of atherosclerosis.
Topics: Aged; Coronary Angiography; Coronary Artery Disease; Female; Humans; Hypolipidemic Agents; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged
PubMed: 31278984
DOI: 10.1016/j.prostaglandins.2019.106345 -
The Journal of International Medical... Oct 2020This study aimed to examine whether oxidized low-density lipoprotein (oxLDL) facilitates platelet aggregation, which is one cause for development of cardiovascular...
OBJECTIVE
This study aimed to examine whether oxidized low-density lipoprotein (oxLDL) facilitates platelet aggregation, which is one cause for development of cardiovascular disease.
METHODS
The susceptibility of platelets to aggregation was monitored by light transmittance aggregometry and a laser light scattering method using low-density lipoprotein (LDL) and oxLDL as agonists. β-thromboglobulin (β-TG) levels released from platelets were also measured after incubation with or without oxLDL.
RESULTS
Platelet aggregation was suppressed by oxLDL as estimated by maximum light transmission. Additionally, adenosine diphosphate-induced further aggregation was slightly reduced by the presence of oxLDL. Aggregation levels of a low number of platelets, which was determined by the laser light scattering method, were lower upon addition of oxLDL compared with unoxidized LDL. After a short time of incubation, oxLDL increased secreted β-TG levels in platelet-rich plasma. However, further incubation with oxLDL caused relatively lower secreted β-TG levels compared with incubation with unoxidized LDL. This fluctuation was not due to β-TG degradation by oxLDL.
CONCLUSIONS
Levels of oxLDL weakly activate platelets at an early stage, but then inhibit platelet function, such as aggregation and β-TG secretion.
Topics: Adenosine Diphosphate; Blood Platelets; Lipoproteins, LDL; Platelet Aggregation
PubMed: 33100088
DOI: 10.1177/0300060520958960 -
JAMA Network Open Oct 2021Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or...
IMPORTANCE
Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Health Sampson equation are not well validated, and data on the accuracy of LDL-C estimation at higher triglyceride levels are limited.
OBJECTIVE
To compare an extended Martin/Hopkins equation for triglyceride values of 400 to 799 mg/dL with the Friedewald and Sampson equations.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study evaluated consecutive patients at clinical sites across the US with patient lipid distributions representative of the US population in the Very Large Database of Lipids from January 1, 2006, to December 31, 2015, with triglyceride levels of 400 to 799 mg/dL. Data analysis was performed from November 9, 2020, to March 23, 2021.
MAIN OUTCOMES AND MEASURES
Accuracy in LDL-C classification according to guideline-based categories and absolute errors between estimated LDL-C and dLDL-C levels. Patients were randomly assigned 2:1 to derivation and validation data sets. Levels of dLDL-C were measured by vertical spin-density gradient ultracentrifugation. The LDL-C levels were estimated using the Friedewald method, with a fixed ratio of triglycerides to very low-density lipoprotein cholesterol (VLDL-C ratio of 5:1), extended Martin/Hopkins equation with a flexible ratio, and Sampson equation with VLDL-C estimation by multiple least-squares regression.
RESULTS
A total of 111 939 patients (mean [SD] age, 52 [13] years; 65.0% male) with triglyceride levels of 400 to 799 mg/dL were included, representing 2.2% of 5 081 680 patients in the database. Across all individual guideline LDL-C classes (<40, 40-69, 70-99, 100-129, 130-159, 160-189, and ≥190), estimation of LDL-C by the extended Martin/Hopkins equation was most accurate (62.1%) compared with the Friedewald (19.3%) and Sampson (40.4%) equations. In classifying LDL-C levels less than 70 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (67.3%) compared with Friedewald (5.1%) and Sampson (26.4%) equations. In addition, for classifying LDL-C levels less than 40 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (57.2%) compared with the Friedewald (4.3%) and Sampson (14.4%) equations. However, considerable underclassification of LDL-C occurred. The magnitude of error between the Martin/Hopkins equation estimation and dLDL-C was also smaller: at LDL-C levels less than 40 mg/dL, 2.7% of patients had 30 mg/dL or greater differences between dLDL-C and estimated LDL-C using the Martin/Hopkins equation compared with the Friedewald (92.5%) and Sampson (38.7%) equations.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study, the extended Martin/Hopkins equation offered greater LDL-C accuracy compared with the Friedewald and Sampson equations in patients with triglyceride levels of 400 to 799 mg/dL. However, regardless of method used, caution is advised with LDL-C estimation in this triglyceride range.
Topics: Adult; Aged; Cohort Studies; Cross-Sectional Studies; Female; Humans; Hyperlipidemias; Lipoproteins, LDL; Male; Middle Aged; Statistics as Topic; Triglycerides; United States
PubMed: 34709388
DOI: 10.1001/jamanetworkopen.2021.28817 -
Current Medical Science Oct 2020It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein (LDL) cholesterol (LDL-C), but its impact on lipoprotein subfractions and...
It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein (LDL) cholesterol (LDL-C), but its impact on lipoprotein subfractions and oxidized low-density lipoprotein (oxLDL) has not been determined. The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein (HDL) as well as oxLDL in untreated patients with coronary atherosclerosis (AS). Thirty-six subjects were enrolled in this study. Of them, 18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls. The plasma lipid profile, lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively. The results showed that pitavastatin treatment indeed not only decreased LDL-C, total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB) levels, and increased HDL cholesterol (HDL-C), but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions. Meanwhile, pitavastatin could decrease plasma oxLDL levels. Furthermore, a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment. We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.
Topics: Adolescent; Adult; Aged; Atherosclerosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Lipoproteins, LDL; Male; Middle Aged; Quinolines; Triglycerides; Young Adult
PubMed: 33123903
DOI: 10.1007/s11596-020-2263-4 -
European Journal of Medicinal Chemistry Dec 2021To construct an artificial low-density lipoprotein (aLDL) that highly mimics low-density lipoprotein (LDL) in vivo, and deliver vincristine (VCR) - doxorubicin (DOX)...
To construct an artificial low-density lipoprotein (aLDL) that highly mimics low-density lipoprotein (LDL) in vivo, and deliver vincristine (VCR) - doxorubicin (DOX) simultaneously, the 100 nm and 35 nm DOX-VCR-aLDLs (DV-aLDLs) were constructed, then the physicochemical characteristics were evaluated. Through in vitro inverse gravity diffusion experiment, the tumour cake and sphere model experiment, draw a conclusion that the diffusion of 35 nm DV-aLDLs was stronger than 100 nm DV-aLDLs, and the tumour retention of 35 nm DV-aLDLs was better than the DV-solution. In addition, the three-dimension (3D) in vivo distribution imaging of aLDLs was performed on HepG-2 tumour-bearing nude mice, followed by the biodistribution and therapeutic efficacy on these xenograft models. Taking advantage of better diffusion capacity in tumour tissue, as well as the synergistic effect of VCR and DOX, the 35 nm DV-aLDL had the strongest efficacy and the lowest toxicity. High entrapment efficiency and stability, both active and passive targeting, making aLDL a potential carrier for tumour-targeted therapy at the same time.
Topics: Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Screening Assays, Antitumor; Female; Hep G2 Cells; Humans; Lipoproteins, LDL; Liver Neoplasms, Experimental; MCF-7 Cells; Mice; Mice, Nude; Molecular Structure; Structure-Activity Relationship; Vincristine
PubMed: 34543934
DOI: 10.1016/j.ejmech.2021.113802 -
Scientific Reports Aug 2023Atherosclerosis is a major cause of cerebral and cardiovascular diseases. Intravascular plaques, a well-known pathological finding of atherosclerosis, have a necrotic...
Atherosclerosis is a major cause of cerebral and cardiovascular diseases. Intravascular plaques, a well-known pathological finding of atherosclerosis, have a necrotic core composed of macrophages and dead cells. Intraplaque macrophages, which are classified into various subtypes, play key roles in maintenance of normal cellular microenvironment. Excessive uptake of oxidized low-density lipoprotein causes conversion of macrophages to foam cells, and consequent progression/exacerbation of atherosclerosis. G-protein-coupled receptor 55 (GPR55) signaling has been reported to associate with atherosclerosis progression. We demonstrated recently that lysophosphatidylglucoside (lysoPtdGlc) is a specific ligand of GPR55, although in general physiological ligands of GPR55 are poorly understood. Phosphatidylglucoside is expressed on human monocytes and can be converted to lysoPtdGlc. In the present study, we examined possible involvement of lysoPtdGlc/GPR55 signaling in foam cell formation. In monocyte-derived M2c macrophages, lysoPtdGlc/GPR55 signaling inhibited translocation of ATP binding cassette subfamily A member 1 to plasma membrane, and cholesterol efflux. Such inhibitory effect was reversed by GPR55 antagonist ML193. LysoPtdGlc/GPR55 signaling in M2c macrophages was involved in excessive lipid accumulation, thereby promoting foam cell formation. Our findings suggest that lysoPtdGlc/GPR55 signaling is a potential therapeutic target for inhibition of atherosclerosis progression.
Topics: Humans; Foam Cells; Cholesterol; Macrophages; Lipoproteins, LDL; Atherosclerosis; Plaque, Atherosclerotic; ATP Binding Cassette Transporter 1; Receptors, Cannabinoid
PubMed: 37544935
DOI: 10.1038/s41598-023-39904-x -
Free Radical Research 2022We have previously demonstrated that low-density lipoprotein (LDL) can be oxidized by iron in the lysosomes of macrophages. Some of the iron content of lysosomes might...
We have previously demonstrated that low-density lipoprotein (LDL) can be oxidized by iron in the lysosomes of macrophages. Some of the iron content of lysosomes might be delivered through autophagy of ferritin (the main iron-storage protein in the body). We have now investigated the effects of ferritin-mediated LDL oxidation on macrophage function. The addition of ferritin to human THP-1 cells and human monocyte-derived macrophages increased lysosomal lipid peroxidation, as shown by LPO-Foam, a fluorescent probe targeted to lysosomes. Incubating THP-1 cells with ferritin and native LDL or LDL aggregated by sphingomyelinase, to allow their endocytosis and delivery to lysosomes, led to the formation of lysosomal ceroid (an advanced lipid oxidation product), indicative of lysosomal LDL oxidation. Incubating THP-1 cells with ferritin and LDL caused metabolic activation of the cells, as shown by increased extracellular acidification and oxygen consumption measured by a Seahorse analyzer. LDL oxidized by ferritin in lysosomes might be released from macrophages when the cells die and lyse and affect neighboring cells in atherosclerotic lesions. Adding LDL oxidized by ferritin at lysosomal pH (pH 4.5) to macrophages increased their intracellular reactive oxygen species formation, shown using dihydroethidium, and increased apoptosis. Ferritin might therefore contribute to LDL oxidation in the lysosomes of macrophages and have atherogenic effects.
Topics: Humans; Lipoproteins, LDL; Ferritins; Lysosomes; Macrophages; Atherosclerosis; Iron
PubMed: 36217887
DOI: 10.1080/10715762.2022.2133703 -
Pharmacological Research Mar 2021Pyroptosis is a form of programmed cell death activated by various stimuli and is characterized by inflammasome assembly, membrane pore formation, and the secretion of... (Review)
Review
Pyroptosis is a form of programmed cell death activated by various stimuli and is characterized by inflammasome assembly, membrane pore formation, and the secretion of inflammatory cytokines (IL-1β and IL-18). Atherosclerosis-related risk factors, including oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals, have been shown to promote pyroptosis through several mechanisms that involve ion flux, ROS, endoplasmic reticulum stress, mitochondrial dysfunction, lysosomal rupture, Golgi function, autophagy, noncoding RNAs, post-translational modifications, and the expression of related molecules. Pyroptosis of endothelial cells, macrophages, and smooth muscle cells in the vascular wall can induce plaque instability and accelerate atherosclerosis progression. In this review, we focus on the pathogenesis, influence, and therapy of pyroptosis in atherosclerosis and provide novel ideas for suppressing pyroptosis and the progression of atherosclerosis.
Topics: Animals; Atherosclerosis; Endothelial Cells; Humans; Immunity, Cellular; Inflammation Mediators; Lipoproteins, LDL; Macrophages; Myocytes, Smooth Muscle; Pyroptosis
PubMed: 33516832
DOI: 10.1016/j.phrs.2021.105447