Reconstitution of lipoproteins. I. Lipid–protein interaction of high density apoproteins, purified apoA-I and apoA-II with dimyristoyl-lecithin and dimyristoyl-lecithin:cholesterol vesicles studied by isomeric spin-labelled lecithins

1980 ◽  
Vol 58 (7) ◽  
pp. 581-591 ◽  
Author(s):  
D. J. Vaughan ◽  
W. C. Breckenridge ◽  
N. Z. Stanacev
Keyword(s):  
Transition Temperature ◽  
Stearic Acid ◽  
High Density Lipoprotein ◽  
Lipid Bilayer ◽  
Weight Ratio ◽  
Density Lipoprotein ◽  
High Density ◽  
Resonance Spectroscopy ◽  
Transition Range ◽  
Temperature Range

Reconstitution of high density lipoprotein-like particles from lecithin, cholesterol, and high density lipoprotein apoproteins was studied. Sonicated mixtures of sn-3-dimyristoyl-lecithin and cholesterol (molar ratio 10:1) were incubated with total human plasma high density apoproteins and purified apoprotein A-I and apoprotein A-II in the presence of isomeric (5′-, 12′-, and 16′-(N-oxyl-4″,4″-dimethyloxazolidine)stearoyl) spin-labelled lecithin probes. The supernatant obtained after centrifugation of the incubation mixture at 12 000× g for 5 min contained reconstituted lipoproteins with an average protein:lipid weight ratio of 0.52–0.53. To determine the position of apoprotein A-I and apoprotein A-II with respect to the lipid bilayer, the thermotropic behaviour of reconstituted lipoproteins was monitored by electron spin resonance spectroscopy using isomeric spin-labelled lecithin probes. Comparison of experimental spectral parameters (transition temperature, temperature range, and cooperative unit) obtained from reconstituted lipoproteins with liposomes of dimyristoyllecithin and dimyristoyllecithin:cholesterol (10:1) showed a relative increase of transition temperature and broadening of the transition range with 5- and 12-(N-oxyl-4′,4′-dimethyloxazolidine)stearic acid containing lecithin probes when reconstituted lipoproteins contained either apoprotein A-I or apoprotein A-II. With 16-(N-oxyl-4′,4′-dimethyloxazolidine)stearic acid containing lecithin probe, the transition temperatures and the temperature range relative to those values measured with 5′- and 12′-(N-oxyl-4″,4″-dimethyloxazolidine) lecithin probes were higher and narrower, respectively, with a tendency towards values obtained for liposomes not containing apoproteins. The cooperative unit in dimyristoyl-lecithin:apoprotein recombinants monitored with 5′- and 12′-(N-oxyl-4″,4″-dimethyloxazolidine) lecithin probes was smaller than or approximately equal to those measured with 16′-(N-oxyl-4″,4″-dimethyloxazolidine) lecithin probes when these systems contained either apoprotein A-I or apoprotein A-II. These and other results indicate that apoproteins A-I and A-II in lipoprotein recombinants of the composition used in our study, are partially embedded within the hydrocarbon portion of the lipid bilayer of reconstituted lipoproteins but do not span the entire lipid bilayer. Relevance of these results to the mechanism of lecithin:cholesterol acyltransferase activation is discussed.

Abstract 3645: Alcohol Volume, Not Drinking Frequency, Increases Plasma High-Density Lipoprotein Sub-Class Particle Concentration

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Linton R Harriss ◽  
Dallas R English ◽  
Rory Wolfe ◽  
Andrew M Tonkin ◽  
Kerin O’Dea ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Alcohol Intake ◽  
Particle Concentration ◽  
Density Lipoprotein ◽  
High Density ◽  
Resonance Spectroscopy ◽  
Cross Sectional ◽  
Men And Women ◽  
Beverage Type ◽  
Drinking Frequency

Introduction: Alcohol intake is positively associated with high-density lipoprotein (HDL) cholesterol, however no studies have investigated the association with lipoprotein sub-classes using nuclear magnetic resonance spectroscopy (NMR). Hypothesis: We assessed the hypothesis that usual daily alcohol intake (volume), beverage type and drinking frequency influence plasma HDL sub-class concentrations as determined by NMR. Methods: Six hundred and ninety volunteers (389 women) aged 40 – 69 years at baseline (1990 –1994) participated in a cross-sectional study using the Melbourne Collaborative Cohort Study, Australia. Measures included self-reported alcohol intake using beverage-specific quantity-frequency questions (volume) and a drinking diary for previous week (frequency). Results: Median alcohol intake was 15.2 g/d (2.7, 32.0) for men and 1.0 g/d (0, 9.6) for women. Alcohol volume was positively associated with total HDL particle concentration in men and women. For men, a 10 g/d increment in alcohol intake increased total HDL particle concentration by 0.62 μmol/L (95% CI: 0.27, 0.98) and small HDL particle concentration by 0.34 μmol/L (0.01, 0.68). For women, total HDL particle concentration increased 1.06 μmol/L (0.60, 1.53) for every 10 g/d increment in alcohol intake. Alcohol volume was positively associated with large HDL particle concentration in premenopausal women [0.67 μmol/L (0.19, 1.15)] and small HDL particle concentration in postmenopausal women [0.82 μmol/L (0.14, 1.51)]. Beer, wine and spirits were all positively associated with total HDL concentration for men. Beer and wine were both positively associated with total HDL concentration for women. Drinking frequency was not associated with total HDL particle concentration or any of its’ sub-classes. Conclusions: Alcohol volume (and not drinking frequency) was positively associated with NMR-determined plasma total HDL particle concentration for men and women. These associations appeared to be regardless of beverage type, although comparison of beverage types was not possible for women. These results suggest that for any given weekly volume of alcohol, the number of drinking days does not influence HDL particle concentration.

Abstract MP36: Changes in High-density Lipoprotein (hdl) Subclasses and Particle Size Over the Menopause Transition are Associated With Higher Levels of Complement Proteins C3 and C4. The Study of Women's Health Across the Nation Hdl Ancillary Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Samar R El Khoudary ◽  
Xirun Chen ◽  
Dan McConnell ◽  
Maria M Brooks ◽  
Trevor Orchard ◽  
...  
Keyword(s):  
Particle Size ◽  
High Density Lipoprotein ◽  
Piecewise Linear ◽  
Density Lipoprotein ◽  
Premenopausal Women ◽  
High Density ◽  
Resonance Spectroscopy ◽  
Mixed Effect ◽  
Complement Proteins ◽  
Menopause Transition

Objective: High density lipoprotein (HDL) is emerging as a key player in modulating inflammation-related response impacting atherosclerosis development. HDL carries multiple proteins with direct roles in complement system activation including C3 and C4. Postmenopausal women have higher levels of C3 than premenopausal women suggesting a role of the menopause transition (MT) in modulating complement proteins. Preliminary work showed significant declines in large HDL particles (HDL-P) and overall HDL particle size, but increases in small HDL-P during the MT. Whether these changes contribute to higher levels of C3 reported after menopause is not known. Our objectives were to test whether C3 and C4 increase around the final menstrual period (FMP) and whether changes in HDL subclasses over the MT associate with C3 and C4 levels in midlife women. Design: We evaluated 558 women (at baseline: age 49.9(2.8) years; 86.6% perimenopausal) who had nuclear magnetic resonance spectroscopy HDL subclasses, C3 and C4 measured up to 5 times over the MT. Piecewise linear mixed-effects models were used to estimate and compare yearly changes in C3 and C4 at 3 time segments relative to the FMP. Linear mixed effect models were used to test associations between changes in each HDL subclass and overall HDL particle size with C3 and C4 separately. Results: Adjusted annual changes in C3 and C4 varied by time segments relative to FMP with significant increases only observed within 1 year before to 2 years after the FMP ( Figure ). These changes were significantly greater than changes in the other 2 time segments. Greater decreases in large and increases in small HDL-P concentrations and decreases in the overall size of HDL-P were independently associated with higher levels of C3 and C4 over time ( Table ). Conclusions: Complement proteins C3 and C4 significantly rise around menopause with C3 showing the steepest rise. Changes in HDL subclasses and overall size over the MT may play role in modulating inflammation responses known to be related to atherosclerosis.

scholarly journals High Density Lipoprotein pathway as a therapeutic target for coronary heart disease: individual participant meta-analysis in 28,597 individuals with 4197 coronary events

2020 ◽  
Author(s):  
Amy R Mulick ◽  
David Prieto-Merino ◽  
Therese Tillin ◽  
Aki Havulinna ◽  
Martin Shipley ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
High Density Lipoprotein ◽  
Longitudinal Studies ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
High Density ◽  
Resonance Spectroscopy ◽  
Chd Risk ◽  
Increased Risk

AbstractImportanceCholesterol content in high-density lipoprotein particles (HDL-C) is associated inversely with coronary heart disease (CHD), but findings from Mendelian randomization studies and randomized trials of HDL-C raising drugs have questioned whether this link is causal. However, these analyses do not exclude a causal role for specific HDL sub-fractions of different density, mobility, size and composition.ObjectiveTo determine whether sub-components of the HDL pathway exhibit differing relationships with CHD risk.DesignIn seven longitudinal studies, we used factor analysis to reduce 21 measures of HDL particle size and lipid content to a smaller number of factors representing different components of the HDL pathway. We constructed factor scores and modelled their associations on CHD risk in adjusted Cox regression analyses. We pooled results using random-effects meta-analysis.SettingSeven population-, individual-, occupational- or community-based longitudinal studies in the UK and Finland.Participants28,597 participants (49% female, mean age 59.6 years) contributed to the analysis.ExposuresSub-components of the HDL pathway, characterized by 21 measures of HDL size and lipid content based on nuclear magnetic resonance spectroscopy.Main OutcomesIncident fatal or non-fatal CHD.ResultsWe identified 4 HDL components with highly replicable across studies; 3 were indices of particle size/composition (extra-large (XL), large (L) and medium/small (MS)), and the other an index of triglycerides (TG) carried in HDL of all sizes. After up to 17 years of follow-up, 4179 incident CHD cases occurred. After adjusting for age, sex, ethnicity, smoking, systolic blood pressure, body mass index, diabetes and LDL-C, higher levels of the XL and MS factors were linked to a reduced risk of CHD (hazard ratio per 1 standard deviation (SD) increase 0.88 [95% CI 0.85, 0.92] and 0.91 [0.87, 0.94]). In contrast, a SD increase in the level of the TG factor was associated with increased risk of CHD (1.10 [1.07, 1.14]).Conclusions and RelevanceWe found qualitative differences between sub-components of the HDL pathway and the risk of developing CHD. Discovery of the biological determinants of these components, possibly through genetic analysis, will facilitate selection of drug targets and inform trial design.Key PointsQuestionCan investigation of sub-components of the high-density lipoprotein (HDL) pathway, measured through nuclear magnetic resonance spectroscopy, point to specific therapeutic targets for prevention of coronary heart disease (CHD)?FindingsUsing individual-level data from seven longitudinal studies including 28,597 participants and 4197 CHD events, we identified two components of the HDL pathway that were associated with reduced, and one that was associated with increased, risk of CHD.MeaningThese sub-components of the HDL pathway, if causally related to atherogenesis, offer a route to more precise therapeutic targets for prevention of CHD.

scholarly journals HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition

2020 ◽  
Author(s):  
Samar R. El Khoudary ◽  
Xirun Chen ◽  
Alexis Nasr ◽  
Jeff Billheimer ◽  
Maria Mori Brooks ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Lipid Content ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Menstrual Period ◽  
Resonance Spectroscopy ◽  
Hdl Function ◽  
Menopause Transition ◽  
And Function

Objective: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. Conclusions: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.

Abstract P101: Premenopausal Life’s Simple 7 Score Is Associated With High-density Lipoprotein Metrics Later In Life: The SWAN HDL Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Alexis Nasr ◽  
Karen A Matthews ◽  
Maria M Brooks ◽  
Trevor Orchard ◽  
Dan McConnell ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Cardiovascular Health ◽  
Menopausal Status ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
High Density ◽  
Resonance Spectroscopy ◽  
Hdl Function ◽  
Life’S Simple 7 ◽  
Life's Simple 7

Objective: In midlife women, higher high-density lipoprotein cholesterol (HDL-C) is not always associated with cardio-protection, suggesting a potential dysfunction of HDL. Novel metrics of HDL may provide further information on its cardio-protective features. The AHA developed the Life’s Simple 7 (LS7) score based on 7 lifestyle factors (cholesterol, BMI, diet, physical activity, smoking, glucose and blood pressure). A higher LS7 indicates a healthier lifestyle and is to cardiovascular health. We aimed to assess if higher premenopausal LS7 score is associated with a protective future HDL metrics profile as measured by greater HDL function (cholesterol efflux capacity), lower HDL-triglycerides (HDL-Tg) and higher HDL-phospholipids (HDL-PL) contents, higher large HDL-particles (HDL-P) and lower small HDL-P levels and larger overall HDL size by nuclear magnetic resonance spectroscopy. Methods: We included 529 women [baseline age 46.4 (2.6) years, 57% (299 of 529) White] from the Study of Women’s Health Across the Nation (SWAN) HDL ancillary study who had premenopausal LS7 score followed by repeated HDL metrics at later visits [time between LS7 score and first HDL measure: 3.9 (1.4) years]. Multivariable linear mixed models were used to analyze the independent association between premenopausal LS7 score and each HDL metric. Results: After adjusting for race, education, and baseline age, menopausal status, economic hardship and high-sensitivity C-reactive protein (Table), higher premenopausal LS7 score was associated with lower HDL-Tg (p<0.0001) and higher HDL-PL (p=0.02), greater total HDL-P (p=0.03), large HDL-P (p=0.0001) and HDL-C (p<0.0001), and larger HDL size (p<0.0001) later in life. Premenopausal LS7 score was not related to HDL function. Conclusion: Higher premenopausal LS7 score was not related to HDL function but related to favorable future HDL contents and subclasses. This indicates that a better premenopausal lifestyle and metabolic health may contribute to a better HDL profile later in life.

Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population

VASA ◽  
2014 ◽  
Vol 43 (3) ◽  
pp. 189-197 ◽  
Author(s):  
Yiqiang Zhan ◽  
Jinming Yu ◽  
Rongjing Ding ◽  
Yihong Sun ◽  
Dayi Hu
Keyword(s):  
High Density Lipoprotein ◽  
Total Cholesterol ◽  
High Density Lipoprotein Cholesterol ◽  
Ankle Brachial Index ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Cholesterol Ratio ◽  
Potential Biomarker

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.

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