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The American Journal of Medicine Sep 2022It is uncertain if lipids or lipoproteins are associated with osteoporotic fractures. In this study, incident hip fracture risk according to conventional lipid levels...
BACKGROUND
It is uncertain if lipids or lipoproteins are associated with osteoporotic fractures. In this study, incident hip fracture risk according to conventional lipid levels and lipoprotein levels and sizes was examined.
METHODS
We followed 5832 participants aged ≥65 years from the Cardiovascular Health Study for hip fracture for a mean of 13.5 (SD 5.7) years. Standard enzymatic methods were used to determine lipid levels (ie, high-density lipoprotein-cholesterol [HDL-c], low-density lipoprotein-cholesterol [LDL-c], and triglycerides). Nuclear magnetic resonance spectroscopy was used to measure lipoprotein fractions (ie, very-low-density lipoprotein-particle [VLDL-P], low-density lipoprotein-particle [LDL-P], high-density lipoprotein-particle [HDL-P]) in a subset of 1849 participants.
RESULTS
We documented 755 incident hip fractures among women (1.19 fractures per 100 participant years [95% confidence interval, 1.04, 1.35]) and 197 among men (0.67 fractures per 100 participant years [95% CI, 0.41, 1.10]) over an average follow-up. HDL-c and LDL-c levels had statistically significant nonlinear U-shaped relationships with hip fracture risk (HDL-c, P = .009; LDL-c, P = .02). Triglyceride levels were not significantly associated with hip fracture risk. In fully adjusted conjoint models, higher VLDL-P concentration (hazard ratio [HR] per 1 standard deviation [SD] increment 1.47 [1.13, 1.91] and size [HR per 1 SD increment 1.24 [1.05, 1.46]) and higher high-density lipoprotein particle size (HR per 1 SD increment 1.81 [1.25, 2.62]) were all associated with higher hip fracture risk.
CONCLUSIONS
Lipids and lipoproteins are associated with hip fracture risk in older adults. The associations are complex. Mechanistic studies are needed to understand these findings.
Topics: Aged; Cholesterol, HDL; Cholesterol, LDL; Female; Hip Fractures; Humans; Lipoproteins; Lipoproteins, LDL; Male; Triglycerides
PubMed: 35679877
DOI: 10.1016/j.amjmed.2022.05.024 -
Clinica Chimica Acta; International... Jul 2011Since Zilversmit first proposed postprandial lipemia as the most common risk of cardiovascular disease, chylomicrons (CM) and CM remnants have been thought to be the... (Review)
Review
Since Zilversmit first proposed postprandial lipemia as the most common risk of cardiovascular disease, chylomicrons (CM) and CM remnants have been thought to be the major lipoproteins which are increased in the postprandial hyperlipidemia. However, it has been shown over the last two decades that the major increase in the postprandial lipoproteins after food intake occurs in the very low density lipoprotein (VLDL) remnants (apoB-100 particles), not CM or CM remnants (apoB-48 particles). This finding was obtained using the following three analytical methods; isolation of remnant-like lipoprotein particles (RLP) with specific antibodies, separation and detection of lipoprotein subclasses by gel permeation HPLC and determination of apoB-48 in fractionated lipoproteins by a specific ELISA. The amount of the apoB-48 particles in the postprandial RLP is significantly less than the apoB-100 particles, and the particle sizes of apoB-48 and apoB-100 in RLP are very similar when analyzed by HPLC. Moreover, CM or CM remnants having a large amount of TG were not found in the postprandial RLP. Therefore, the major portion of the TG which is increased in the postprandial state is composed of VLDL remnants, which have been recognized as a significant risk for cardiovascular disease.
Topics: Animals; Chylomicrons; Humans; Lipoproteins, VLDL
PubMed: 21531214
DOI: 10.1016/j.cca.2011.04.018 -
Journal of Atherosclerosis and... Jan 2023We established automated assay kits for quantifying small dense low-density lipoprotein (sdLDL)-cholesterol (C), LDL-triglyceride (TG), and high-density lipoprotein...
AIMS
We established automated assay kits for quantifying small dense low-density lipoprotein (sdLDL)-cholesterol (C), LDL-triglyceride (TG), and high-density lipoprotein (HDL)3-C, and apolipoprotein (apo)E-rich HDL-C, and these have been recognized as sensitive biomarkers for predicting coronary artery disease. We investigated the circadian rhythms of these novel lipids to determine if fasting is required to determine basal levels.
METHODS
Forty-eight inpatients with type 2 diabetes and 19 healthy volunteers were studied. Blood samples were collected at seven time points, which were obtained after an overnight fast, before and 2 h after each meal, and before the next breakfast. sdLDL-C, LDL-TG, remnant-like particle (RLP)-C, TG-rich lipoprotein (TRL-C), HDL3-C, and apoE-rich HDL-C were measured by the homogeneous methods. NonHDL-C, large buoyant (lb)LDL-C and HDL2-C were calculated by subtracting sdLDL-C from LDL-C or HDL3-C from HDL-C, respectively.
RESULTS
Serum TG levels were significantly increased after meals in both healthy participants and patients with diabetes. RLP-C and TRL-C were also increased postprandially. LDL-TG, LDL-C, nonHDL-C, HDL2,3-C, and apoE-rich HDL-C did not exhibit significant fluctuation during the day in healthy participants and patients with diabetes. sdLDL-C was slightly increased postprandially in subjects with diabetes (1-2 mg/dl, 3%-9%), though its increase was not significant compared to the baseline (fasting) level. Significant postprandial reduction was observed with LDL-C and lbLDL-C. There was no influence of statin therapy or oral anti-diabetes drugs on the circadian rhythm of LDL-C subspecies.
CONCLUSIONS
Subtle postprandial increase in sdLDL-C is considered a negligible level in general clinical practice. Fasting is not mandatory to measure basal concentrations of LDL and HDL subspecies.
Topics: Humans; Cholesterol, LDL; Diabetes Mellitus, Type 2; Cholesterol, HDL; Healthy Volunteers; Triglycerides; Lipoproteins, HDL; Apolipoproteins E; Circadian Rhythm
PubMed: 35249932
DOI: 10.5551/jat.63383 -
The Journal of Clinical Investigation Jun 1990
Comparative Study Review
Topics: Apolipoproteins; Cardiovascular Diseases; Chromosome Mapping; Humans; Lipoprotein(a); Lipoproteins; Phylogeny; Plasminogen; Risk Factors; Solubility
PubMed: 2140835
DOI: 10.1172/JCI114625 -
Lipids in Health and Disease Jun 2022An excessive rise in maternal lipids during pregnancy may have detrimental impacts on maternal and fetal health leading to adverse pregnancy outcomes. However, knowledge...
BACKGROUND
An excessive rise in maternal lipids during pregnancy may have detrimental impacts on maternal and fetal health leading to adverse pregnancy outcomes. However, knowledge gaps exist with respect to the association between lipid biomarkers and birth outcomes.
METHODS
We conducted a secondary data analysis of healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22-28 weeks of gestation and birth outcome data. Serum was analyzed for conventional lipid profile (total-C, HDL-C, LDL-C, and triglycerides) and lipoprotein subclass distribution, including particle number (nM) and size (nm), for very low-density lipoprotein (VLDL)/chylomicron (CM), low density lipoprotein (LDL), and high-density lipoprotein (HDL), by nuclear magnetic resonance spectroscopy. Associations between maternal lipids and birth outcomes, including birth weight (g) and gestational age (weeks), were assessed using multivariable linear regression, adjusted for pre-pregnancy BMI.
RESULTS
Although conventional lipids were not associated (p > 0.05) with birth outcomes, every 1-unit increment in large VLDL/CM particles (nM) and VLDL/CM size (nm) was associated with an increase in birth weight (confounder-adjusted β-coefficient, 45.80 g [5.30, 86.20, p = 0.003] and 24.90 g [8.80, 40.90, p = 0.002], respectively). Among the HDL subclass parameters, a 1-unit (nM) increase in the concentration of total HDL-particles was associated with a reduced birth weight (confounder adjusted β-coefficient, -19.40 g [95% confidence interval, -36.70, -2.20]; p = 0.03) after adjustment for maternal pre-pregnancy BMI.
CONCLUSION
The preliminary results of this pilot study suggest that total particle concentrations of VLDL/CM and HDL in mid-pregnancy have divergent associations with birth weight, potentially reflecting the specific roles of these lipoprotein particles with respect to placental function and fetal growth.
Topics: Birth Weight; Chylomicrons; Female; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, VLDL; Particle Size; Parturition; Pilot Projects; Placenta; Pregnancy; Triglycerides
PubMed: 35698189
DOI: 10.1186/s12944-022-01664-4 -
Current Atherosclerosis Reports Mar 2021The term high density lipoproteins (HDL) refers to an eclectic collection of subparticles that play diverse roles in physiology. Here, we define the term "HDL... (Review)
Review
PURPOSE OF REVIEW
The term high density lipoproteins (HDL) refers to an eclectic collection of subparticles that play diverse roles in physiology. Here, we define the term "HDL subspecies" and review recent work on their molecular characterization and relation to disease, focusing on cardiovascular disease and diabetes.
RECENT FINDINGS
The HDL family contains over 200 proteins and nearly 200 lipids that partition into different particles in plasma. Simple subfractionation of HDL based on a particular physicochemical property has not risen to the challenge of revealing the roles of specific particles in disease. However, by targeting minor protein or lipid components, a handful of compositionally defined HDL subspecies have been described and characterized. By combining targeted particle isolation techniques with the power of large human studies, progress is being made in understanding HDL subspecies functions and implications for disease. However, much work remains before these advancements can be translated into disease mitigation strategies.
Topics: Cardiovascular Diseases; Diabetes Mellitus; Humans; Lipids; Lipoproteins; Lipoproteins, HDL
PubMed: 33772657
DOI: 10.1007/s11883-021-00925-4 -
Current Drug Targets Mar 2008High plasma levels of the apo-B-containing lipoproteins are casually implicated in the pathogenesis of atherosclerosis. This finding, backed by decades of animal and... (Review)
Review
High plasma levels of the apo-B-containing lipoproteins are casually implicated in the pathogenesis of atherosclerosis. This finding, backed by decades of animal and human studies, has sparked interest in defining which classes of apo-B-containing lipoprotein particles are most atherogenic. Although small LDL particles and larger remnant lipoproteins both appear to be atherogenic, it has been difficult to discern which particles are the most atherogenic. Here, we summarize several mouse models that have provided insights into this issue. The influence of lipoprotein size on susceptibility to atherosclerosis was examined by studying the phenotypes of two strains of mice with virtually identical levels of plasma cholesterol--Ldlr(-/-)Apob(100/100) and Apoe(-/-) Apob(100/100) mice. The Ldlr(-/-) Apob(100/100) mice, where the cholesterol is in small LDL particles, had far more atherosclerosis than Apoe(-/-) Apob(100/100) mice, where virtually all of the cholesterol was in larger, VLDL-sized particles. Another intriguing animal model is the Gpihbp1-deficient mouse. GPIHBP1 is an endothelial cell platform for lipolysis, and mice lacking this protein have an accumulation of large, triglyceride-rich lipoproteins. Defining the extent of atherosclerosis in these mice should provide new insights into the atherogenicity of large, triglyceride-rich lipoproteins.
Topics: Animals; Animals, Genetically Modified; Atherosclerosis; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Lipoproteins; Mice
PubMed: 18336235
DOI: 10.2174/138945008783755629 -
Clinical and Translational Science Mar 2022Amiodarone and its main metabolite, desethylamiodarone (DEA), are highly distributed to serum lipoproteins such as very-low-density lipoprotein (VLDL) and low-density...
Amiodarone and its main metabolite, desethylamiodarone (DEA), are highly distributed to serum lipoproteins such as very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), which are the carriers of triglyceride and cholesterol. This study aimed to investigate the association of serum concentrations of amiodarone and DEA with the levels of serum lipids in terms of drug distribution to lipoprotein fractions in patients with hyperlipidemia. Total serum concentrations of amiodarone and DEA were examined in 116 patients receiving amiodarone for tachyarrhythmias. The concentration-to-dose (C/D) ratio of amiodarone positively correlated with the level of serum triglyceride (r = 0.541, p < 0.001) and was higher in the hypertriglyceridemic state than in normotriglyceridemic state (479 ± 211 vs. 320 ± 161, p < 0.001). No correlation was found between the C/D ratio of DEA and serum triglyceride levels (r = 0.272), although higher values were observed in the hypertriglyceridemic state (322 ± 125 vs. 285 ± 143, p < 0.001). In the hypertriglyceridemic state, the distribution of amiodarone increased in LDL/VLDL fraction and decreased in high-density lipoprotein and albumin fractions. The ratio of serum amiodarone to serum DEA, a metabolic ratio of amiodarone, positively correlated with serum triglyceride levels (r = 0.572, p < 0.001) and was higher in the hypertriglyceridemic state, suggesting that amiodarone metabolism decreased in hyperlipidemia. The results of this study reveal that serum concentrations of amiodarone increase in the hypertriglyceridemic state through the increased lipoprotein-binding and decreased metabolism of amiodarone.
Topics: Amiodarone; Humans; Hyperlipidemias; Lipoproteins; Lipoproteins, LDL; Lipoproteins, VLDL; Triglycerides
PubMed: 34786846
DOI: 10.1111/cts.13199 -
Biological Chemistry May 2021Triglyceride hydrolysis by lipoprotein lipase (LPL), regulated by apolipoproteins C-II (apoC-II) and C-III (apoC-III), is essential for maintaining normal lipid...
Triglyceride hydrolysis by lipoprotein lipase (LPL), regulated by apolipoproteins C-II (apoC-II) and C-III (apoC-III), is essential for maintaining normal lipid homeostasis. During triglyceride lipolysis, the apoCs are known to be transferred from very low-density lipoprotein (VLDL) to high-density lipoprotein (HDL), but the detailed mechanisms of this transfer remain unclear. In this study, we investigated the extent of the apoC transfers and their distribution in HDL subfractions, HDL2 and HDL3. Each HDL subfraction was incubated with VLDL or biotin-labeled VLDL, and apolipoproteins and lipids in the re-isolated HDL were quantified using western blotting and high-performance liquid chromatography (HPLC). In consequence, incubation with VLDL showed the increase of net amount of apoC-II and apoC-III in the HDL. HPLC analysis revealed that the biotin-labeled apolipoproteins, including apoCs and apolipoprotein E, were preferably transferred to the larger HDL3. No effect of cholesteryl ester transfer protein inhibitor on the apoC transfers was observed. Quantification of apoCs levels in HDL2 and HDL3 from healthy subjects (n = 8) showed large individual differences between apoC-II and apoC-III levels. These results suggest that both apoC-II and apoC-III transfer disproportionately from VLDL to HDL2 and the larger HDL3, and these transfers might be involved in individual triglyceride metabolism.
Topics: Apolipoprotein C-II; Apolipoprotein C-III; Healthy Volunteers; Humans; Lipoproteins, HDL2; Lipoproteins, HDL3; Lipoproteins, LDL
PubMed: 33934596
DOI: 10.1515/hsz-2020-0288 -
Philosophical Transactions of the Royal... Oct 2015Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins... (Review)
Review
Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins are synthesized in precursor form with an N-terminal signal sequence (SS) that targets translocation across the cytoplasmic or inner membrane (IM). Lipid modification and SS processing take place at the periplasmic face of the IM. Outer membrane (OM) lipoproteins take the localization of lipoproteins (Lol) export pathway, which ends with the insertion of the N-terminal lipid moiety into the inner leaflet of the OM. For many lipoproteins, the biogenesis pathway ends here. We provide examples of lipoproteins that adopt complex topologies in the OM that include transmembrane and surface-exposed domains. Biogenesis of such lipoproteins requires additional steps beyond the Lol pathway. In at least one case, lipoprotein sequences reach the cell surface by being threaded through the lumen of a beta-barrel protein in an assembly reaction that requires the heteropentomeric Bam complex. The inability to predict surface exposure reinforces the importance of experimental verification of lipoprotein topology and we will discuss some of the methods used to study OM protein topology.
Topics: Bacterial Outer Membrane Proteins; Cell Membrane; Gram-Negative Bacteria; Lipoproteins; Models, Biological; Models, Molecular; Protein Processing, Post-Translational; Protein Transport
PubMed: 26370942
DOI: 10.1098/rstb.2015.0030