UNASSIGNED: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis.
UNASSIGNED: Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS.
UNASSIGNED: Individuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21-1.53), factor 3 (OR:1.75, 95 %CI:1.53-2.02) and factor 4 (OR:1.49; 95 %CI:1.32-1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77-0.97) and factor 5 (OR:0.74, 95 %CI:0.65-0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82-61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14-9.29) and HDL (OR:0.35, 95 %CI:0.13-0.72) were confirmed.
UNASSIGNED: Large TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS.

Extracellular vesicles (EVs) in blood plasma are recognized as potential biomarkers for disease. Although blood plasma is easily obtainable, analysis of EVs at the single particle level is still challenging due to the biological complexity of this body fluid. Besides EVs, plasma contains different types of lipoproteins particles (LPPs), that outnumber EVs by orders of magnitude and which partially overlap in biophysical properties such as size, density and molecular makeup. Consequently, during EV isolation LPPs are often co-isolated. Furthermore, physical EV-LPP complexes have been observed in purified EV preparations. Since co-isolation or association of LPPs can impact EV-based analysis and biomarker profiling, we investigated the presence and formation of EV-LPP complexes in biological samples by using label-free atomic force microscopy, cryo-electron tomography and synchronous Rayleigh and Raman scattering analysis of optically trapped particles and fluorescence-based high sensitivity single particle flow cytometry. Furthermore, we evaluated the impact on flow cytometric analysis in the presence of LPPs using in vitro spike-in experiments of purified tumour cell line-derived EVs in different classes of purified human LPPs. Based on orthogonal single-particle analysis techniques we demonstrate that EV-LPP complexes can form under physiological conditions. Furthermore, we show that in fluorescence-based flow cytometric EV analysis staining of LPPs, as well as EV-LPP associations, can influence quantitative and qualitative EV analysis. Lastly, we demonstrate that the colloidal matrix of the biofluid in which EVs reside impacts their buoyant density, size and/or refractive index (RI), which may have consequences for down-stream EV analysis and EV biomarker profiling.

OBJECTIVE: Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia are tightly entangled. The objective of this study was to assess the relations between a broad panel of inflammatory biomarkers and lipoprotein subclass parameters.
METHODS: We utilized data from the population-based Study of Health in Pomerania (SHIP-TREND, n = 403). Plasma concentrations of 37 inflammatory markers were measured by a bead-based assay. Furthermore, we employed nuclear magnetic resonance spectroscopy to measure total cholesterol, total triglycerides, total phospholipids as well as the fractional concentrations of cholesterol, triglycerides, phospholipids, ApoA1, ApoA2 and ApoB in all major lipoprotein subclasses. Associations between inflammatory biomarkers and lipoprotein subclasses were analyzed by adjusted linear regression models.
RESULTS: APRIL, BAFF, TWEAK, sCD30, Pentraxin-3, sTNFR1, sTNFR2, Osteocalcin, Chitinase 3-like 1, IFN-alpha2, IFN-gamma, IL-11, IL-12p40, IL-29, IL-32, IL-35, TSLP, MMP1 and MMP2 were related with lipoprotein subclass components, forming two distinct clusters. APRIL had inverse relations to HDL-C (total and subclasses) and HDL Apo-A1 and Apo-A2 content. MMP-2 was inversely related to VLDL-C (total and subclasses), IDL-C as well as LDL5/6-C and VLDL-TG, IDL-TG, total triglycerides as well as LDL5/5-TG and HDL4-TG. Additionally, we identified a cluster of cytokines linked to the Th1-immune response, which were associated with an atherogenic lipoprotein profile.
CONCLUSIONS: Our findings expand the existing knowledge of inflammation-lipoprotein interactions, many of which are suggested to be involved in the pathogeneses of chronic non-communicable diseases. The results of our study support the use of immunomodulatory substances for the treatment and possibly prevention of CVD.

We present for consideration a hypothesis that impaired movement of lipoprotein particles in the extracellular space in the brain in ageing is central to and causes all the key pathophysiological features of Alzheimer\'s disease (AD). The role of lipoprotein particles is to transport cholesterol from glial cells, where it is synthesised, to neurons, which require cholesterol for synaptic plasticity. The lipoprotein particles have a cholesterol-containing hydrophobic core, in which amyloid-β (Aβ) can be solubilised. The core is surrounded by a hydrophilic surface containing apolipoprotein E (APOE) which, as neurons bear receptors for APOE, determines the destination of the particles. The problem arises because the extracellular space is a narrow cleft, barely wider than the lipoprotein particles themselves, which they have to navigate in order to perform their crucial cholesterol-transporting function. We explain how lipoprotein particles could become trapped in the ageing extracellular matrix and that this primary abnormality results in reduced delivery of cholesterol to neurons leading to impaired synaptic plasticity, crucial for learning and memory. It can also explain extracellular Aβ accumulation, to which a microglial response generates a neurotoxic reaction, and intraneuronal tau aggregation, each of which exacerbate the problem. All these players have been known for many years to be important in Alzheimer\'s pathogenesis but a single unifying mechanism to explain how they are linked has been lacking. This proposed mechanism, with entrapment of lipoproteins particles as key to the development of AD, can explain the failure of so many clinical trials and points out new directions to be taken.

Lipoprotein particles (LPs) are excellent transporters and have been intensively studied in cardiovascular diseases, especially regarding parameters such as their class distribution and accumulation, site-specific delivery, cellular internalization, and escape from endo/lysosomal compartments. The aim of the present work is the hydrophilic cargo loading of LPs. As an exemplary proof-of-principle showcase, the glucose metabolism-regulating hormone, insulin, was successfully incorporated into high-density lipoprotein (HDL) particles. The incorporation was studied and verified to be successful using Atomic Force Microscopy (AFM) and Fluorescence Microscopy (FM). Single-molecule-sensitive FM together with confocal imaging visualized the membrane interaction of single, insulin-loaded HDL particles and the subsequent cellular translocation of glucose transporter type 4 (Glut4).

OBJECTIVE: Experimental studies report that intermediate-density lipoprotein (IDL), the precursor of low-density lipoprotein, promotes atherosclerotic plaque formation. However, whether IDL is involved in the development of atherosclerosis in humans is still unclear. The aim of this community-based study is to examine the association between IDL particle (IDL-P) concentrations and the 5-year progression of carotid atherosclerosis.
METHODS: Baseline IDL-P concentrations were measured using nuclear magnetic resonance spectroscopy in 927 participants aged 45-74 years with no history of cardiovascular disease (CVD) at baseline. To estimate the association between baseline IDL-P concentrations and 5-year progression of carotid atherosclerosis, indicated by atherosclerotic plaque progression and changes in total plaque area (TPA), multivariable-adjusted regression was employed.
RESULTS: During the 5-year follow-up period, 45.8% of participants developed new plaques. Baseline IDL-P concentrations were significantly associated with the progression of carotid atherosclerosis. Participants in the highest quartile of IDL-P concentrations exhibited 1.36-fold (95% confidence interval [CI]: 1.09-1.68) increased progression of carotid plaque and 1.67-fold (95% CI: 1.04-2.69) higher TPA than those in the lowest quartile. These relationships were independent of baseline concentrations of low-density lipoprotein particles and very-low-density lipoprotein particles and their subclasses.
CONCLUSIONS: Elevated IDL-P concentrations were independently associated with the progression of carotid atherosclerosis, suggesting that IDL-P is a novel risk factor for the development of atherosclerosis.

Intake of dairy fat within the matrix of cheese lowered circulating LDL cholesterol concentration to a greater extent than the same components consumed separately as butter, protein, and calcium. However, circulating LDL cholesterol is not indicative of concentration or size of LDL particles (LDL-P), which are recognized as more sensitive risk markers of CVD.
This was an exploratory analysis to investigate the role of the food matrix on lipoprotein particle size distribution, after a dairy fat intervention, in overweight adults aged ≥50 y.
Lipoprotein particle size distribution was measured in fasting EDTA blood samples taken at week 0 (baseline) and at week 6, using NMR. In total, 127 participants (BMI ≥ 25 kg/m2, aged ≥50 y) received ∼42 g dairy fat in 1 of 4 treatments: group A, 120 g full-fat cheddar cheese (FFCC); group B, reduced-fat cheese plus butter (RFC+B); group C, butter, calcium caseinate powder, and calcium supplement (CaCO3) (BCC); or group D, 120 g FFCC (as per group A) but after a 6-wk washout period during which they excluded cheese before intervention.
Total VLDL and chylomicron particles (VLDL/CM-P) decreased after intervention. There was a strong correlation between reduced VLDL/CM-P and a reduction in small proatherogenic VLDL-P (r = 0.888, P < 0.001). Reductions in total LDL-P were associated with a reduction in small LDL-P and, to a lesser extent, with large LDL-P. There was a significant main effect of treatment for change in intermediate-density lipoprotein particles (IDL-P) after the intervention (P = 0.023) between groups B and D (-46.86 ± 30.38 and 40.69 ± 32.72 nmol/L, respectively). HDL particle (HDL-P) parameters (diameter, concentration, or size distribution) were not affected by diet.
Our findings indicate that reductions in LDL cholesterol observed with dairy fat consumption are driven by reductions in LDL-P concentration. A trend toward a less atherogenic profile was observed, but there was no clear effect of the individual food matrices. This trial was registered at ISRCTN as ISRCTN86731958.

BACKGROUND: A 10-month strategy of cardiac telerehabilitation (CTR) improved outcomes over a standard centre-based cardiac rehabilitation (CBCR), as recently published. We hypothesised that prolonged telerehabilitation could also improve proinflammatory status and lipoprotein particle composition.
METHODS: A randomised controlled trial compared a prolonged CTR program with CBCR in post-ACS patients. Patient\'s age was 18-72 years with low-risk criteria. Blood samples were drawn at baseline, at 4- and 10-months follow-up. Advanced lipoprotein characterization was performed using the NMR-based Liposcale test. Signals from glycoproteins (GlycA and GlycB) were also assessed.
RESULTS: The final analysis included 31 patients in the CTR group and 25 patients in the CBCR group. GlycA decreased in the CTR group (p = 0,007). LDL particle number (LDL-P) increase in both groups, but it was at the expense of small-sized LDL in the CBCR group (p = 0.012). Triglycerides in intermediate-density lipoprotein (IDL-TG) increased only in the CBCR group (p = 0.043). The triglyceride-to-HDL (TG/HDL) ratio decreased only in the CTR group (p = 0.006). The TG/HDL ratio was correlated with GlycA (Spearman\'s correlation coefficient: 0.558, p < 0.001) but not with CRP (p = 0.101).
CONCLUSIONS: Our results showed that a 10-month CTR program reduced GlycA levels, the TG/HDL ratio and avoided unfavourable long-term changes in lipoprotein particle composition. Registration at http://ClinicalTrials.gov. NCT number: 04942977.

UNASSIGNED: Systematic inflammation and lipid profiles are two major therapeutic targets for cardiovascular diseases. The effect of a nutritionally balanced vegan diet on systematic inflammation and lipoprotein subclass awaits further examination.
UNASSIGNED: To investigate the change in novel and traditional cardiometabolic risk factors before and after a dietitian-led vegan program, and to test the bioavailability of vitamin B12 in Taiwanese purple laver as part of a vegan diet.
UNASSIGNED: A one-arm pilot intervention study.
UNASSIGNED: Nine patients with dyslipidemia participated in this 12-week vegan program.
UNASSIGNED: Nuclear Magnetic Resonance (NMR) detected GlycA signals (systematic inflammation) and lipoprotein subclass (atherogenicity); trimethylamine N-oxide (TMAO); and other cardiometabolic risk factors.
UNASSIGNED: Wilcoxon signed-rank test.
UNASSIGNED: In this 12-week vegan intervention emphasizing whole foods, systematic inflammation improved as indicated by a reduction in GlycA (median: -23 μmol/L, p = 0.01). LDL-c (low-density lipoprotein cholesterol) (median -24 mg/dl, p = 0.04) and LDL-p (low-density lipoprotein particles) (median -75 nmol/L, p = 0.02) both decreased significantly. VLDL (very-low-density lipoprotein) and chylomicron particles showed a decreasing trend (-23.6 nmol/L, p = 0.05). Without caloric restriction, body mass index (BMI) (-0.7 kg/m2, p = 0.03), waist circumferences (-2.0 cm, p < 0.001), HbA1c (-0.2%, p = 0.02), and (HOMA-IR) homeostatic model assessment for insulin resistance (-0.7, p = 0.04) have all improved. The change in the TMAO and vitamin B12 status as measured by holo-transcobalamin appeared to depend on baseline diets, TMAO, and vitamin B12 status.
UNASSIGNED: A dietitian-led vegan program may improve systematic inflammation and other novel and traditional cardiometabolic risk factors in high-risk individuals.

Cholesterol is one of the main constituents of plasma membranes; thus, its supply is of utmost importance. This review covers the known mechanisms of cholesterol transfer from circulating lipoprotein particles to the plasma membrane, and vice versa. To achieve homeostasis, the human body utilizes cellular de novo synthesis and extracellular transport particles for supply of cholesterol and other lipids via the blood stream. These lipoprotein particles can be classified according to their density: chylomicrons, very low, low, and high-density lipoprotein (VLDL, LDL, and HDL, respectively). They deliver and receive their lipid loads, most importantly cholesterol, to and from cells by several redundant routes. Defects in one of these pathways (e.g., due to mutations in receptors) usually are not immediately fatal. Several redundant pathways, at least temporarily, compensate for the loss of one or more of them, but the defects trigger systemic diseases, such as atherosclerosis later on. Recently, intracellular membrane-membrane contact sites were shown to be involved in intracellular cholesterol transfer and the plasma membrane itself has been proposed to act as a binding site for lipoprotein-mediated cargo unloading.