Apolipoproteins as potential communicators play an essential role in the pathogenesis and treatment of early atherosclerosis.

Atherosclerosis as the leading cause of the cardiovascular disease is closely related to cholesterol deposition within subendothelial areas of the arteries. Significantly, early atherosclerosis intervention is the critical phase for its reversal. As atherosclerosis progresses, early foam cells formation may evolve into fibrous plaques and atheromatous plaque, ulteriorly rupture of atheromatous plaque increases risks of myocardial infarction and ischemic stroke, resulting in high morbidity and mortality worldwide. Notably, amphiphilic apolipoproteins (Apos) can concomitantly combine with lipids to form soluble lipoproteins that have been demonstrated to associate with atherosclerosis. Apos act as crucial communicators of lipoproteins, which not only can mediate lipids metabolism, but also can involve in pro-atherogenic and anti-atherogenic processes of atherosclerosis via affecting subendothelial retention and aggregation of low-density lipoprotein (LDL), oxidative modification of LDL, foam cells formation and reverse cholesterol transport (RCT) in macrophage cells. Correspondingly, Apos can be used as endogenous and/or exogenous targeting agents to effectively attenuate the development of atherosclerosis. The article reviews the classification, structure, and relationship between Apos and lipids, how Apos serve as communicators of lipoproteins to participate in the pathogenesis progression of early atherosclerosis, as well as how Apos as the meaningful targeting mass is used in early atherosclerosis treatment.

Effects of CaCl2 on the structure of high-density lipoprotein and low-density lipoprotein isolated from rapidly salted separated egg yolk.

According to previous research, adding CaCl2 to the salting solution improves the quality of salted separated egg yolk. To further understand the improvement mechanism of CaCl2, this paper investigated the effect of CaCl2 on the structure of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) during the salting process. The results indicated that the addition of CaCl2 can affect the composition of HDL and LDL apolipoproteins, improving the orderliness of the HDL structure and the looseness of the LDL structure. It was discovered by atomic force microscopy (AFM) that adding CaCl2 to the salting solution can weaken the aggregation behavior of HDL. Simultaneously, the addition of CaCl2 decreased the relative content of intermolecular ß-sheets in the secondary structure of HDL and LDL, influenced their tertiary conformation, and prevented HDL and LDL from participating in the formation of a three-dimensional gel structure by influencing their hydrogen bonds and hydrophobic interactions.

Oxidized Low-Density Lipoprotein (Ox-LDL)-Triggered Double-Lock Probe for Spatiotemporal Lipoprotein Oxidation and Atherosclerotic Plaque Imaging.

Low-density lipoprotein (LDL), especially oxidative modified LDL (Ox-LDL), is the key risk factor for plaque accumulation and the development of cardiovascular disease. Herein, a highly specific Ox-LDL-triggered fluorogenic-colorimetric probe Pro-P1 is developed for visualizing the oxidation and aggregation progress of lipoproteins and plaque. A series of green fluorescent protein chromophores with modified donor-acceptor structures, containing carbazole as an electron donor and various substituents including pyridine-vinyl (P1), phenol-vinyl (P2), N, N-dimethylaniline-vinyl (P3), and thiophene-vinyl (P4), have been synthesized and evaluated. Emission spectroscopy and theoretical calculations of P1-P4 indicate that P1 shows enhanced green fluorescence (λem = 560 nm) by inhibiting its twisted intramolecular charge transfer in the presence of Ox-LDL. This feature allows the selection of P1 as a sensitive probe to directly visualize ferroptosis and Cu2+ -mediated LDL oxidative aggregation via in situ formation of fluorophore-bound Ox-LDL in living cells. The red-emissive probe Pro-P1 (λem = 660 nm) is prepared via borate protection of P1, which can be cleaved into P1 under high expression of HOCl and Ox-LDL condition at the lesion site, resulting in enhanced green emission. The plaque area and size with clear boundaries can be delineated by colorimetric fluorescence imaging and fluorescence lifetime imaging with precise differentiation.

Ultrasound-assisted pH-shifting to construct a stable aqueous solution of paprika oleoresin using egg yolk low-density lipoprotein as a natural liposome-like nano-emulsifier.

In this study, a stable aqueous solution of paprika oleoresin (PO, the natural colorant extracted from the fruit peel of Capsicum annuum L) was constructed. The solubility of PO in an alkline aqueous solution (pH 10.95-11.10) increased rapidly. However, the aqueous solution of PO (pH 12.00) was unstable, obvious stratification was observed, and the color retention rate was only 52.99% after 28 days of storage. Chicken egg yolk low-density lipoprotein (LDL) was added combined with ultrasonic treatment to improve the stability of LDL-PO solution. The method could decrease the turbidity by 17.5 %, reduce the average particle size of the LDL-PO solution (13.9%), and enhance the interaction and combination of LDL and PO. The prepared PO aqueous solution was used in yogurt, egg white gel, fish balls and soymilk, and it could significantly improve the color of products and provided potential health benefits.

Elevated LDL Triglycerides and Atherosclerotic Risk.

BACKGROUND: It is unclear whether elevated low-density lipoprotein (LDL) triglycerides are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). OBJECTIVES: This study tested the hypothesis that elevated LDL triglycerides are associated with an increased risk of ASCVD and of each ASCVD component individually. METHODS: The study investigators used the Copenhagen General Population Study, which measured LDL triglycerides in 38,081 individuals with a direct automated assay (direct LDL triglycerides) and in another 30,208 individuals with nuclear magnetic resonance (NMR) spectroscopy (NMR LDL triglycerides). Meta-analyses aggregated the present findings with previously reported results. RESULTS: During a median follow-up of 3.0 and 9.2 years, respectively, 872 and 5,766 individuals in the 2 cohorts received a diagnosis of ASCVD. Per 0.1 mmol/L (9 mg/dL) higher direct LDL triglycerides, HRs were 1.26 (95% CI: 1.17-1.35) for ASCVD, 1.27 (95% CI: 1.16-1.39) for ischemic heart disease, 1.28 (95% CI: 1.11-1.48) for myocardial infarction, 1.22 (95% CI: 1.08-1.38) for ischemic stroke, and 1.38 (95% CI: 1.21-1.58) for peripheral artery disease. Corresponding HRs for NMR LDL triglycerides were 1.26 (95% CI: 1.20-1.33), 1.33 (95% CI: 1.25-1.41), 1.41 (95% CI: 1.31-1.52), 1.13 (95% CI: 1.05-1.23), and 1.26 (95% CI: 1.10-1.43), respectively. The foregoing results were not entirely statistically explained by apolipoprotein B levels. In meta-analyses for the highest quartile vs the lowest quartile of LDL triglycerides, random-effects risk ratios were 1.50 (95% CI: 1.35-1.66) for ASCVD (4 studies; 71,526 individuals; 8,576 events), 1.62 (95% CI: 1.37-1.93) for ischemic heart disease (6 studies; 107,538 individuals; 9,734 events), 1.30 (95% CI: 1.13-1.49) for ischemic stroke (4 studies; 78,026 individuals; 4,273 events), and 1.53 (95% CI: 1.29-1.81) for peripheral artery disease (4 studies; 107,511 individuals; 1,848 events). CONCLUSIONS: Elevated LDL triglycerides were robustly associated with an increased risk of ASCVD and of each ASCVD component individually in 2 prospective cohort studies and in meta-analyses of previous and present studies combined.

Effect of crocin on glycated human low-density lipoprotein: A protective and mechanistic approach.

Human low-density lipoprotein (LDL) is known to have a role in coronary artery diseases when it undergoes modification due to hyperglycaemic conditions. Plant products like crocin play an essential role in protecting against oxidative stress and in the production of advanced glycation end-products (A.G.E.s). In this study, the anti-glycating effect of crocin was analyzed using various biochemical, spectroscopic, and in silico approaches. Glycation-mediated oxidative stress was confirmed by nitroblue tetrazolium, carbonyl content, and lipid peroxidation assays, and it was efficiently protected by crocin in a concentration-dependent manner. A.N.S. fluorescence, thioflavin T (ThT) assay, and electron microscopy confirmed that the structural changes in LDL during glycation lead to the formation of fibrillar aggregates, which can be minimized by crocin treatment. Moreover, secondary structural perturbations in LDL were observed using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), where crocin was found to prevent the loss of secondary structure in glycated LDL. Spectroscopic studies like U.V. absorbance, fluorescence spectroscopy, CD, FTIR, and fluorescence resonance energy transfer (FRET) provided insights into the interaction mechanism between LDL and crocin. Molecular docking supports these results with a highly negative binding energy of -10.3 kcal/mol, suggesting the formation of a stable ldl-crocin complex. Our study indicates that crocin may be a potent protective agent against coronary artery diseases by limiting the glycation of LDL in people with such disorders.

Simple emulsion template method towards self-anticoagulant and high-efficiency carboxymethyl chitosan-based adsorbent for low-density lipoprotein from whole blood.

In this study, carboxymethyl chitosan (CMCS)-based double cross-linked network spheres, are constructed by an emulsion template method. The first crosslinking network comes from the chelation between the CMCS and zinc ions, while the second one is based on the covalent crosslinking of 2-acrylamido-2-methyl-1-propanesulfonicacid (AMPS); and the as-prepared spheres are termed as ECMCS@AMPSs. The emulsion template method endows the ECMCS@AMPSs with large pore area (58.3 m2/g) and ultra-high porosity (92.3 %). Thanks to the heparin-mimicking functional groups of -OH, -COO- and -SO3-, the ECMCS@AMPSs show excellent anticoagulant properties without the activation of the complement system, contact system and platelets. Compared with the spheres without emulsification, the porous structure of the ECMCS@AMPSs results in a 5.3-fold increase in low-density lipoprotein (LDL) adsorption capacity in hypercholesterolemia plasma. Most importantly, in vitro simulated hemoperfusion experiment shows that the cumulative adsorption capacity of LDL by the ECMCS@AMPSs is as high as 41.66 mg/g in 1 h, which is approximately 4.2 times that of high-density lipoprotein (HDL). In conclusion, the ECMCS@AMPSs with self-anticoagulant and high-efficiency adsorption of LDL fabricated via simple emulsion template method have great clinical application prospects in the field of lipoprotein apheresis.

A New Structural Model of Apolipoprotein B100 Based on Computational Modeling and Cross Linking.

ApoB-100 is a member of a large lipid transfer protein superfamily and is one of the main apolipoproteins found on low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) particles. Despite its clinical significance for the development of cardiovascular disease, there is limited information on apoB-100 structure. We have developed a novel method based on the "divide and conquer" algorithm, using PSIPRED software, by dividing apoB-100 into five subunits and 11 domains. Models of each domain were prepared using I-TASSER, DEMO, RoseTTAFold, Phyre2, and MODELLER. Subsequently, we used disuccinimidyl sulfoxide (DSSO), a new mass spectrometry cleavable cross-linker, and the known position of disulfide bonds to experimentally validate each model. We obtained 65 unique DSSO cross-links, of which 87.5% were within a 26 Å threshold in the final model. We also evaluated the positions of cysteine residues involved in the eight known disulfide bonds in apoB-100, and each pair was measured within the expected 5.6 Å constraint. Finally, multiple domains were combined by applying constraints based on detected long-range DSSO cross-links to generate five subunits, which were subsequently merged to achieve an uninterrupted architecture for apoB-100 around a lipoprotein particle. Moreover, the dynamics of apoB-100 during particle size transitions was examined by comparing VLDL and LDL computational models and using experimental cross-linking data. In addition, the proposed model of receptor ligand binding of apoB-100 provides new insights into some of its functions.

Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis.

BACKGROUND: Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis. OBJECTIVES: The authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants. METHODS: The authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr-/-) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization. RESULTS: LO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging, and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr-/- mice, in the vicinity of macrophages. CONCLUSIONS: The authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.

Antioxidant interactions among hydrophilic and lipophilic dietary phytochemicals based on inhibition of low-density lipoprotein and DNA damage.

Antioxidant interaction among hydrophilic phytochemicals (caffeic acid, p-coumaric acid) and lipophilic phytochemicals (ß-carotene, lycopene) in different mole ratios (n/n, 1:9, 3:7, 5:5, 7:3, 9:1) was evaluated. Assays performed were based on the scavenging activity of hydrogen peroxide (H2 O2 ), the inhibition of low-density lipoprotein oxidation (ox-LDL) and DNA damage in vitro, using isobological analysis, synergistic rate (SR), and combination index (CI). Results showed that groups containing higher ratios of hydrophilic phytochemicals exhibited synergism while those containing higher ratios of lipophilic phytochemicals showed antagonism. Meanwhile, groups containing caffeic acid (e.g., caffeic acid:ß-carotene, 9:1) with more hydroxyl groups showed higher synergism (SR = 0.76 ± 0.02, CI = 0.77 ± 0.03) than groups containing p-coumaric acid (e.g., p-coumaric acid:ß-carotene, 9:1, SR = 0.88 ± 0.04, CI = 0.82 ± 0.05) on the scavenging activity of H2 O2 . Groups that contained lycopene (caffeic acid: lycopene, 9:1) with a higher ability of regeneration by phenolic acids showed more significant synergism (SR = 0.70 ± 0.02, CI = 0.79 ± 0.03) than groups containing ß-carotene (e.g., caffeic acid:ß-carotene, 9:1, SR = 1.00 ± 0.03, CI = 0.98 ± 0.04) on the inhibition of DNA damage. This study provided a basis for antioxidant interactions among phytochemicals against ox-LDL and DNA damage in vivo. In addition, the choice of appropriate ratios and structures of hydrophilic and lipophilic phytochemicals should be considered in the diet and formulation of functional foods.

Amphiphilic shell nanomagnetic adsorbents for selective and highly efficient capture of low-density lipoprotein from hyperlipidaemia serum.

Removal of low-density lipoprotein (LDL) from hyperlipemia patients' blood represents an effective approach to prevent the progression of atherosclerotic cardiovascular disease. Based on the LDL structural characteristics and intermolecular interactions, a tailored nano-adsorbent (Fe3O4@SiO2@PAA-PE) was prepared aimed at the removal of LDL from hyperlipemia serum with high selectivity. The core-shell structured magnetic nanoparticles were embedded in an amphiphilic layer composed of hydrophilic poly(acrylic acid) and lipophilic phospholipids to provide multifunctional binding for LDL particles. The results of dynamic light scattering, water contact angle and zeta-potential measurements, thermal gravimetric analysis, and X-ray photoelectron spectroscopy together with Fourier transform infrared spectroscopy confirmed the core-shell structured nanoparticles bearing amphiphilic poly acrylic acid and phospholipid molecules. Because of the superior electronegativity of the functional layer, the nano-adsorbent demonstrated favorable adsorption selectivity against high-density lipoprotein, which possesses a similar structure to LDL but has a cardio-protective function in the human body. The respective adsorption capacity of Fe3O4@SiO2@PAA-PE towards LDL, total cholesterol and triglycerides reached up to 6.26 mg g-1, 8.41 mg g-1 and 9.19 mg g-1, which was 7.03, 9.45 and 10.32 times that towards HDL (0.89 mg g-1). The kinetic and isothermal studies revealed that multiple interactions containing both physical and chemical adsorption occurred in the binding procedure between LDL and Fe3O4@SiO2@PAA-PE, and chemical adsorption may play a more predominant role in LDL adsorption. The nano-adsorbent also had negligible effects on blood cells, and possessed satisfactory recyclability, low cytotoxicity and hemolysis ratios, indicating its good application prospects as a hemoperfusion adsorbent in the treatment of hyperlipidaemia.

OxLDL induces membrane structure rearrangement leading to biomechanics alteration and migration deficiency in macrophage.

Cholesterol sequestration from plasma membrane has been shown to induce lipid packing disruption, causing actin cytoskeleton reorganization and polymerization, increasing cell stiffness and inducing lysosomal exocytosis in non-professional phagocytes. Similarly, oxidized form of low-density lipoprotein (oxLDL) has also been shown to disrupt lipid organization and packing in endothelial cells, leading to biomechanics alterations that interfere with membrane injury and repair. For macrophages, much is known about oxLDL effects in cell activation, cytokine production and foam cell formation. However, little is known about its impact in the organization of macrophage membrane structured domains and cellular mechanics, the focus of the present study. Treatment of bone marrow-derived macrophages (BMDM) with oxLDL not only altered membrane structure, and potentially the distribution of raft domains, but also induced actin rearrangement, diffuse integrin distribution and cell shrinkage, similarly to observed upon treatment of these cells with MßCD. Those alterations led to decreased migration efficiency. For both treatments, higher co-localization of actin cytoskeleton and GM1 was observed, indicating a similar mechanism of action involving raft-like domain dynamics. Lastly, like MßCD treatment, oxLDL also induced lysosomal spreading in BMDM. We propose that OxLDL induced re-organization of membrane/cytoskeleton complex in macrophages can be attributed to the insertion of oxysterols into the membrane, which lead to changes in lipid organization and disruption of membrane structure, similar to the effect of cholesterol depletion by MßCD treatment. These results indicate that oxLDL can induce physical alterations in the complex membrane/cytoskeleton of macrophages, leading to significant biomechanical changes that compromise cell behavior.

Probe ultrasonification of egg yolk plasma forms low-density lipoprotein nanoparticles that efficiently protect canine semen during cryofreezing.

Around the world, many couples have turned to in vitro fertilization as a viable solution to fertility issues. Low-density lipoprotein (LDL) is a protein best known for transporting fat molecules throughout the body, but it has also been shown to protect sperm cells during cryopreservation due to its micellar structure. In the present study, we aimed to evaluate different protocols for the preparation of nanoparticles from egg yolk plasma (EYP) containing LDL to improve the viability of cryopreserved canine semen. EYP was subjected to three distinct treatments: ultrasonification in an ultrasound bath at 40 kHz for 30 min (LDL-B); ultrasonification via an ultrasound probe at 50% amplitude for 30 min (LDL-P); and high-pressure homogenization at 10,000 PSI for six cycles (LDL-H). Sperm quality was assessed after thawing using computer-assisted sperm analysis and flow cytometry. The results revealed that compared to the EYP control, the LDL-P formulation presented significantly higher efficiency (p < 0.05) in maintaining total and progressive sperm motility, sperm membrane integrity and fluidity, and levels of intracellular reactive oxygen species. The LDL-P nanoparticles had an average size of approximately 250 nm, a PDI value of 0.3, and -1.15 mV of zeta potential, which are very important because it is an indicator of the stability of a colloidal dispersion. Therefore, we conclude that ultrasonication of EYP using a probe is an efficient method for the preparation of LDL nanoparticles that would enhance the cryoprotection of semen during freezing.

Biomembrane-mimetic hemoperfusion adsorbent for efficient removal of low-density lipoprotein from hyperlipemia blood.

Lowering of low-density lipoprotein (LDL) levels in blood of patients with hyperlipidaemia can effectively prevent the progression of atherosclerosis and coronary heart disease. The present study demonstrated a facile synthesis strategy to prepare biomembrane-mimetic LDL adsorbent (PVA@COOH-PE) via directional immobilization of phospholipid onto macro-porous cross-linked poly(vinyl alcohol) spheres. The binding between the prepared adsorbent and LDL particles simulates the cytosolic lipid droplets to form a lipid-packing structure. The adsorbent possesses satisfactory removal efficiency for LDL and total cholesterol (TCH) in hyperlipemia serum, while remains high-density lipoprotein (HDL) concentration within the normal range. The adsorption capacities for LDL and TCH are about 1.13 and 1.74 mg/ml respectively, which are nearly three and four times higher than that of HDL (0.42 mg/ml). The adsorbent also possesses satisfactory anticoagulant properties, causes negligible effect on blood cells and produces low hemolysis ratios. The excellent blood compatibility plus LDL removal efficiency of PVA@COOH-PE indicates its good application prospect as hemoperfusion adsorbent in the treatment of hyperlipidaemia.

Purification and Analysis of Circulating Lipid Particles.

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.

Nitrogen-doped carbon dots/Ni-MnFe-layered double hydroxides (N-CDs/Ni-MnFe-LDHs) hybrid nanomaterials as immunoassay label for low-density lipoprotein detection.

Nitrogen-doped carbon dots/Ni-MnFe-layered double hydroxides (N-CDs/Ni-MnFe-LDHs) are demonstrated as superior peroxidase mimic antibody labels alternative to horseradish peroxidase (HRP) in an immunoassay, potentially overcoming some of the inherent disadvantages of HRP and other enzyme mimicking nanomaterials. They revealed efficient peroxidase-like activity and catalyzed the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to form the intense blue product (at 620 nm) in the presence of hydrogen peroxide (H2O2). Using low-density lipoprotein (LDL) as a model target, an ultra-low limit of detection (0.0051 mg/dL) and a linear range of 0.0625-0.750 mg/dL were achieved, exhibiting higher sensitivity than the HRP-based immunoassay. Thus, the proposed N-CDs/Ni-MnFe-LDHs can be used as HRP mimicking analogs for developing highly sensitive colorimetric immunosensors for detection of biomarkers, as well as trace chemical analysis.

The Initial Human Atherosclerotic Lesion and Lipoprotein Modification-A Deep Connection.

Atherosclerosis research typically focuses on the evolution of intermediate or advanced atherosclerotic lesions rather than on prelesional stages of atherogenesis. Yet these early events may provide decisive leads on the triggers of the pathologic process, before lesions become clinically overt. Thereby, it is mandatory to consider extracellular lipoprotein deposition at this stage as the prerequisite of foam cell formation leading to a remarkable accumulation of LDL (Low Density Lipoproteins). As progression of atherosclerosis displays the characteristic features of a chronic inflammatory process on the one hand and native LDL lacks inflammatory properties on the other hand, the lipoprotein must undergo biochemical modification to become atherogenic. During the last 25 years, evidence was accumulated in support of a different concept on atherogenesis proposing that modification of native LDL occurs through the action of ubiquitous hydrolytic enzymes (enzymatically modified LDL or eLDL) rather than oxidation and contending that the physiological events leading to macrophage uptake and reverse transport of eLDL first occur without inflammation (initiation with reversion). Preventing or reversing initial atherosclerotic lesions would avoid the later stages and therefore prevent clinical manifestations. This concept is in accordance with the response to retention hypothesis directly supporting the strategy of lowering plasma levels of atherogenic lipoproteins as the most successful therapy for atherosclerosis and its sequelae. Apart from but unquestionable closely related to this concept, there are several other hypotheses on atherosclerotic lesion initiation favoring an initiating role of the immune system ('vascular-associated lymphoid tissue' (VALT)), defining foam cell formation as a variant of lysosomal storage disease, relating to the concept of the inflammasome with crystalline cholesterol and/or mitochondrial DAMPs (damage-associated molecular patterns) being mandatory in driving arterial inflammation and, last but not least, pointing to miRNAs (micro RNAs) as pivotal players. However, direct anti-inflammatory therapies may prove successful as adjuvant components but will likely never be used in the absence of strategies to lower plasma levels of atherogenic lipoproteins, the key point of the perception that atherosclerosis is not simply an inevitable result of senescence. In particular, given the importance of chemical modifications for lipoprotein atherogenicity, regulation of the enzymes involved might be a tempting target for pharmacological research.

Lipoprotein subtypes after testosterone therapy in transmasculine adolescents.

Differences in lipoprotein-particle subclasses between men and women start in puberty and narrow after menopause, suggesting a role for sex steroids. In this cross-sectional cohort study, we examined lipoprotein subtype profiles in transmasculine adolescents treated with testosterone. Transmasculine adolescents (n = 17) had lipoprotein profiles that were similar to those of cisgender males (n = 33) and more atherogenic than those of cisgender females (n = 32), with higher concentrations of small low-density lipoprotein (LDL) particles (435 ± 222 nmol/L vs. 244 ± 163 nmol/L, p = 0.008) and lower concentrations of large high-density lipoprotein (HDL) particles (1.5 ± 1.3 µmol/L vs 2.7 ± 1.2 µmol/L, p = 0.003) when compared to cisgender females. Thus, testosterone appears to be a major contributor to differences in lipoprotein profiles, a surrogate for cardiovascular disease risk, between cisgender women and both transgender and cisgender men.

Vincristine-doxorubicin co-loaded artificial low-density lipoproteins towards solid tumours.

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.

The effects of fat consumption on low-density lipoprotein particle size in healthy individuals: a narrative review.

Cardiovascular disease (CVD) is the number one contributor to death in the United States and worldwide. A risk factor for CVD is high serum low-density lipoprotein cholesterol (LDL-C) concentrations; however, LDL particles exist in a variety of sizes that may differentially affect the progression of CVD. The small, dense LDL particles, compared to the large, buoyant LDL subclass, are considered to be more atherogenic. It has been suggested that replacing saturated fatty acids with monounsaturated and polyunsaturated fatty acids decreases the risk for CVD. However, certain studies are not in agreement with this recommendation, as saturated fatty acid intake did not increase the risk for CVD, cardiovascular events, and/or mortality. Furthermore, consumption of saturated fat has been demonstrated to increase large, buoyant LDL particles, which may explain, in part, for the differing outcomes regarding fat consumption on CVD risk. Therefore, the objective was to review intervention trials that explored the effects of fat consumption on LDL particle size in healthy individuals. PubMed and Web of Science were utilized during the search process for journal articles. The results of this review provided evidence that fat consumption increases large, buoyant LDL and/or decreases small, dense LDL particles, and therefore, influences CVD risk.