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Circulation Mar 2024Cholesterol efflux capacity (CEC) predicts cardiovascular disease independently of high-density lipoprotein (HDL) cholesterol levels. Isolated small HDL particles are...
BACKGROUND
Cholesterol efflux capacity (CEC) predicts cardiovascular disease independently of high-density lipoprotein (HDL) cholesterol levels. Isolated small HDL particles are potent promoters of macrophage CEC by the ABCA1 (ATP-binding cassette transporter A1) pathway, but the underlying mechanisms are unclear.
METHODS
We used model system studies of reconstituted HDL and plasma from control and lecithin-cholesterol acyltransferase (LCAT)-deficient subjects to investigate the relationships among the sizes of HDL particles, the structure of APOA1 (apolipoprotein A1) in the different particles, and the CECs of plasma and isolated HDLs.
RESULTS
We quantified macrophage and ABCA1 CEC of 4 distinct sizes of reconstituted HDL. CEC increased as particle size decreased. Tandem mass spectrometric analysis of chemically cross-linked peptides and molecular dynamics simulations of APOA1, the major protein of HDL, indicated that the mobility of C-terminus of that protein was markedly higher and flipped off the surface in the smallest particles. To explore the physiological relevance of the model system studies, we isolated HDL from LCAT-deficient subjects, whose small HDLs (like reconstituted HDLs) are discoidal and composed of APOA1, cholesterol, and phospholipid. Despite their very low plasma levels of HDL particles, these subjects had normal CEC. In both the LCAT-deficient subjects and control subjects, the CEC of isolated extra-small HDL (a mixture of extra-small and small HDL by calibrated ion mobility analysis) was 3- to 5-fold greater than that of the larger sizes of isolated HDL. Incubating LCAT-deficient plasma and control plasma with human LCAT converted extra-small and small HDL particles into larger particles, and it markedly inhibited CEC.
CONCLUSIONS
We present a mechanism for the enhanced CEC of small HDLs. In smaller particles, the C-termini of the 2 antiparallel molecules of APOA1 are "flipped" off the lipid surface of HDL. This extended conformation allows them to engage with ABCA1. In contrast, the C-termini of larger HDLs are unable to interact productively with ABCA1 because they form a helical bundle that strongly adheres to the lipid on the particle. Enhanced CEC, as seen with the smaller particles, predicts decreased cardiovascular disease risk. Thus, extra-small and small HDLs may be key mediators and indicators of the cardioprotective effects of HDL.
Topics: Humans; Apolipoprotein A-I; Cardiovascular Diseases; Lipoproteins, HDL; Cholesterol; ATP Binding Cassette Transporter 1; Macrophages; Cholesterol, HDL
PubMed: 38018436
DOI: 10.1161/CIRCULATIONAHA.123.065959 -
European Review For Medical and... Dec 2023Patients with pancreatic diseases are at increased risk of cardiovascular events. Investigating various apolipoprotein forms as important atherogenesis components may...
OBJECTIVE
Patients with pancreatic diseases are at increased risk of cardiovascular events. Investigating various apolipoprotein forms as important atherogenesis components may improve cardiovascular risk (CVR) prediction. This study aimed to investigate CVR factors in patients with chronic pancreatitis.
PATIENTS AND METHODS
The study enrolled 70 patients (40 males and 30 females, mean age 55.2 years) with chronic pancreatitis and treated pancreatic exocrine insufficiency. We assessed CVR by apolipoproteins A-I, A-II, B, and C-III, lipid profile; score systems [SCORE risk chart and Framingham Risk Score (FRS)], diabetes mellitus; chronic pancreatitis by M-ANNHEIM classification. Statistics were performed via SPSS v. 22.
RESULTS
Low apolipoprotein A-I and high apolipoprotein B levels with increased atherogenic potential were observed in 37 and 26 patients. 45.71% demonstrated a high risk of myocardial infarction with high apolipoprotein B/apolipoprotein A-I ratio. Men are at higher CVR risk. Apolipoproteins A-I and A-II correlated with the cardioprotective high-density lipoprotein (HDL) in contrast to apolipoproteins B and C-III, which correlated strongly with low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG). Increased CVR assessed by FRS correlated with significantly lower apolipoprotein A-I and higher apolipoprotein B and apolipoprotein B/apolipoprotein A-I ratio. With the increase in chronic pancreatitis severity, we observed decreased apolipoproteins and increased apolipoprotein B/apolipoprotein A-I ratio.
CONCLUSIONS
Apolipoproteins are valuable CVR indicators. Further studies are required to establish a CVR screening panel in this population.
Topics: Male; Female; Humans; Middle Aged; Apolipoprotein A-I; Cardiovascular Diseases; Risk Factors; Apolipoproteins; Apolipoproteins B; Triglycerides; Atherosclerosis; Heart Disease Risk Factors; Pancreatitis, Chronic; Cholesterol, HDL
PubMed: 38164866
DOI: 10.26355/eurrev_202312_34802 -
Alzheimer's Research & Therapy Dec 2022Alzheimer's disease (AD) shares risk factors with cardiovascular disease (CVD) and dysregulated cholesterol metabolism is a mechanism common to both diseases....
BACKGROUND
Alzheimer's disease (AD) shares risk factors with cardiovascular disease (CVD) and dysregulated cholesterol metabolism is a mechanism common to both diseases. Cholesterol efflux capacity (CEC) is an ex vivo metric of plasma high-density lipoprotein (HDL) function and inversely predicts incident CVD independently of other risk factors. Cholesterol pools in the central nervous system (CNS) are largely separate from those in blood, and CNS cholesterol excess may promote neurodegeneration. CEC of cerebrospinal fluid (CSF) may be a useful measure of CNS cholesterol trafficking. We hypothesized that subjects with AD and mild cognitive impairment (MCI) would have reduced CSF CEC compared with Cognitively Normal (CN) and that CSF apolipoproteins apoA-I, apoJ, and apoE might have associations with CSF CEC.
METHODS
We retrieved CSF and same-day ethylenediaminetetraacetic acid (EDTA) plasma from 108 subjects (40 AD; 18 MCI; and 50 CN) from the Center for Neurodegenerative Disease Research biobank at the Perelman School of Medicine, University of Pennsylvania. For CSF CEC assays, we used N9 mouse microglial cells and SH-SY5Y human neuroblastoma cells, and the corresponding plasma assay used J774 cells. Cells were labeled with [H]-cholesterol for 24 h, had ABCA1 expression upregulated for 6 h, were exposed to 33 μl of CSF, and then were incubated for 2.5 h. CEC was quantified as percent [H]-cholesterol counts in medium of total counts medium+cells, normalized to a pool sample. ApoA-I, ApoJ, ApoE, and cholesterol were also measured in CSF.
RESULTS
We found that CSF CEC was significantly lower in MCI compared with controls and was poorly correlated with plasma CEC. CSF levels of ApoJ/Clusterin were also significantly lower in MCI and were significantly associated with CSF CEC. While CSF ApoA-I was also associated with CSF CEC, CSF ApoE had no association with CSF CEC. CSF CEC is significantly and positively associated with CSF Aβ. Taken together, ApoJ/Clusterin may be an important determinant of CSF CEC, which in turn could mitigate risk of MCI and AD risk by promoting cellular efflux of cholesterol or other lipids. In contrast, CSF ApoE does not appear to play a role in determining CSF CEC.
Topics: Humans; Mice; Animals; Clusterin; Alzheimer Disease; Apolipoprotein A-I; Neurodegenerative Diseases; Neuroblastoma; Apolipoproteins E; Cholesterol; Cardiovascular Diseases
PubMed: 36572909
DOI: 10.1186/s13195-022-01119-z -
Medicine Jul 2022Postoperative delirium is a common complication for elderly patients. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage with... (Observational Study)
Observational Study
Postoperative delirium is a common complication for elderly patients. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage with postoperative delirium. Although it has been implicated that serum apolipoprotein levels might be associated with senile cognitive disorder, its role in the development of delirium has not been fully investigated. This study examined the association of apolipoproteins with delirium after surgery. This was a post hoc analysis of 117 patients who participated in a prospective observational study of delirium in patients undergoing cancer surgery. Patients were clinically assessed for delirium within the first 5 days of surgery. Serum levels of apolipoprotein A-I, B, and E were measured on postoperative day 3. Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Serum levels of apolipoprotein A-I and B were increased in patients with delirium whereas those of apolipoprotein E were decreased. These changes in apolipoprotein A-I and E levels were associated with the presence of phosphorylated neurofilament heavy subunit in the serum, and were significantly associated with delirium (A-I: adjusted odds ratio [aOR], 6.238; 95% confidence interval [CI], 2.766-20.68; P < .0001; E: aOR, 0.253; 95% CI, 0.066-0.810; P = .0193). A combination of apolipoprotein A-I and E offers significant discrimination between delirium and nondelirium with high accuracy (area under the curve, 0.8899). Serum apolipoprotein A-I and E levels were associated with delirium and the presence of phosphorylated neurofilament heavy subunit in serum. Therefore, apolipoproteins might be useful biomarkers of postoperative delirium.
Topics: Aged; Apolipoprotein A-I; Biomarkers; Delirium; Humans; Postoperative Complications; Prospective Studies; Risk Factors
PubMed: 35905282
DOI: 10.1097/MD.0000000000029906 -
Journal of Lipid Research Apr 2024Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed...
Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed to explore the causal effects of lipid traits on both all-cause and cause-specific mortality. One-sample Mendelian randomization (MR) with linear and nonlinear assumptions was conducted in a cohort of 407,951 European participants from the UK Biobank. Six lipid traits, consisting of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were included to investigate the causal associations with mortality. Two-sample MR was performed to replicate the association between each lipid trait and all-cause mortality. Univariable MR results showed that genetically predicted higher ApoA1 was significantly associated with a decreased all-cause mortality risk (HR[95% CI]:0.93 [0.89-0.97], P value = 0.001), which was validated by the two-sample MR analysis. Higher lipoprotein(a) was associated with an increased risk of all-cause mortality (1.03 [1.01-1.04], P value = 0.002). Multivariable MR confirmed the direct causal effects of ApoA1 and lipoprotein(a) on all-cause mortality. Meanwhile, nonlinear MR found no evidence for nonlinearity between lipids and all-cause mortality. Our examination into cause-specific mortality revealed a suggestive inverse association between ApoA1 and cancer mortality, a significant positive association between lipoprotein(a) and cardiovascular disease mortality, and a suggestive positive association between lipoprotein(a) and digestive disease mortality. High LDL-C was associated with an increased risk of cardiovascular disease mortality but a decreased risk of neurodegenerative disease mortality. The findings suggest that implementing interventions to raise ApoA1 and decrease lipoprotein(a) levels may improve overall health outcomes and mitigate cancer and digestive disease mortality.
Topics: Humans; Mendelian Randomization Analysis; Male; Female; Lipids; Middle Aged; Risk Factors; Apolipoprotein A-I; Lipoprotein(a); Cause of Death; Aged
PubMed: 38458338
DOI: 10.1016/j.jlr.2024.100528 -
Arteriosclerosis, Thrombosis, and... Oct 2023Impaired cholesterol efflux capacity (CEC) is a novel lipid metabolism trait associated with atherosclerotic cardiovascular disease. Mechanisms underlying CEC variation...
BACKGROUND
Impaired cholesterol efflux capacity (CEC) is a novel lipid metabolism trait associated with atherosclerotic cardiovascular disease. Mechanisms underlying CEC variation are unknown. We evaluated associations of circulating metabolites with CEC to advance understanding of metabolic pathways involved in cholesterol efflux regulation.
METHODS
Participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) who underwent nuclear magnetic resonance metabolome profiling and CEC measurement (N=3543) at baseline were included. Metabolite associations with CEC were evaluated using standard linear regression analyses. Repeated ElasticNet and multilayer perceptron regression were used to assess metabolite profile predictive performance for CEC. Features important for CEC prediction were identified using Shapley Additive Explanations values.
RESULTS
Greater CEC was significantly associated with metabolite clusters composed of the largest-sized particle subclasses of VLDL (very-low-density lipoprotein) and HDL (high-density lipoprotein), as well as their constituent apo A, apo A, phospholipid, and cholesterol components (β=0.072-0.081; <0.001). Metabolite profiles had poor accuracy for predicting in vitro CEC in linear and nonlinear analyses (R<0.02; Spearman ρ<0.18). The most important feature for CEC prediction was race, with Black participants having significantly lower CEC compared with other races.
CONCLUSIONS
We identified independent associations among CEC, the largest-sized particle subclasses of VLDL and HDL, and their constituent apolipoproteins and lipids. A large proportion of variation in CEC remained unexplained by metabolites and traditional clinical risk factors, supporting further investigation into genomic, proteomic, and phospholipidomic determinants of CEC.
Topics: Humans; Cholesterol, HDL; Proteomics; Lipoproteins, HDL; Cholesterol; Atherosclerosis; Apolipoproteins A
PubMed: 37615111
DOI: 10.1161/ATVBAHA.122.318222 -
The Journal of Sexual Medicine Mar 2021Erectile dysfunction (ED) is closely related to coronary heart disease (CHD). Apolipoprotein (Apo) A1, Apo B, and Apo A/Apo B are known to be predictive factors for CHD....
BACKGROUND
Erectile dysfunction (ED) is closely related to coronary heart disease (CHD). Apolipoprotein (Apo) A1, Apo B, and Apo A/Apo B are known to be predictive factors for CHD. They are not yet a definite laboratory marker for the diagnosis of ED in cardiology. Therefore, we investigated the association between Apo A1, Apo B, and Apo A/Apo B, and ED.
AIM
To investigate the association between Apo A, Apo B, and Apo A/Apo B and the severity of ED.
METHODS
A total of 152 ED patients and 39 healthy control participants underwent a fasting blood draw to test for Apo A, Apo B, and Apo A/Apo B and a detailed laboratory examination. The International Erectile Function Index (IIEF-5) was used to determine the severity of ED. Receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff values for Apo A, Apo B, and Apo A/Apo B. Each questionnaire was completed before any diagnosis was made or treatment performed.
OUTCOMES
Several lipid profile indicators (Apo A, Apo B, Apo A/Apo B, lipoprotein (a), free fatty acids, and total cholesterol) were studied, along with several questionnaires.
RESULTS
In our study, the number of patients with no ED, mild ED, mild-to-moderate ED, and moderate-to-severe ED were 39 (20.4%), 58 (30.4%), 36 (18.8%), and 58 (30.4%), respectively. Apo A and Apo A/Apo B were significantly reduced in patients with more severe ED (P = .037 and P < .001, respectively), while Apo B was significantly increased in patients with more severe ED (P = .002). According to the ROC curve, Apo A/Apo B had a medium diagnostic value for risk of ED with an AUC of 0.743 (95% CI: 0.68-0.80). For moderate-to-severe ED, 3 apolipoprotein indexes, including Apo B, Apo A, and Apo A/Apo B had medium diagnostic performance with AUCs of 0.759 (95% CI: 0.66-0.84), 0.703 (95% CI: 0.60-0.79), and 0.808 (95% CI: 0.72-0.88), respectively.
CLINICAL IMPLICATIONS
Our results can inform cardiologists in the assessment of ED in patients with CHD.
STRENGTHS AND LIMITATIONS
This study is the first to investigate the association between apolipoprotein and ED in China. The major limitations are that our sample size was too small to have matched controls without ED for different Apo levels.
CONCLUSION
Our results showed that Apo B, Apo A, and Apo A/Apo B can be used as markers to evaluate the risk of ED and that these proteins play an important role in the etiology of ED. Li X, Li D. The Suggestive Effect of Apo A, Apo B, and Apo A/Apo B on Erectile Dysfunction. J Sex Med 2021;18:448-456.
Topics: Apolipoprotein B-100; Apolipoproteins A; Apolipoproteins B; China; Erectile Dysfunction; Humans; Male; Penile Erection; Risk Factors
PubMed: 33423974
DOI: 10.1016/j.jsxm.2020.12.004 -
Complementary Therapies in Medicine Aug 2023Numerous approaches have been assigned to treat dyslipidemia (DLP). Turmeric/curcumin have been widely investigated with this regard. In the current study, we explored... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Numerous approaches have been assigned to treat dyslipidemia (DLP). Turmeric/curcumin have been widely investigated with this regard. In the current study, we explored the effect of curcumin/turmeric supplementation on lipid profile.
METHODS
Online databases were searched up to October 2022. The outcomes included triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), apolipoprotein B (Apo-B), and apolipoprotein A (Apo-A). We used the Cochrane quality assessment tool to evaluate the risk of bias. The effect sizes were estimated as weighted mean difference (WMD) and 95% confidence intervals (CIs).
RESULTS
Out of 4182 articles retrieved from the initial search, 64 randomized clinical trials (RCTs) were included in the study. Between-study heterogeneity was significant. Meta-analysis showed that turmeric/curcumin supplementation exerts statistically significant improvements on blood levels of TC (WMD = -3.99 mg/dL; 95% CI = -5.33, -2.65), TG (WMD = -6.69 mg/dL; 95% CI = -7.93, -5.45), LDL-c (WMD = -4.89 mg/dL; 95% CI = -5.92, -3.87), and HDL-c (WMD = 1.80 mg/dL; 95% CI = 1.43, 2.17). However, turmeric/curcumin supplementation was not associated with improvements in blood levels of Apo-A or Apo-B. The studies did not thoroughly address the issues of potency, purity, or consumption with other foods.
CONCLUSION
Turmeric/curcumin supplementation seems to be effective in improving blood levels of TC, TG, LDL-c, and HDL-c; but may not be capable of improving their pertinent apolipoproteins. Since the evidence was assessed to be low and very low concerning the outcomes, these findings should be dealt with caution.
Topics: Humans; Apolipoproteins A; Cholesterol, HDL; Cholesterol, LDL; Curcuma; Curcumin; Dietary Supplements; Lipids; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 37230418
DOI: 10.1016/j.ctim.2023.102955 -
Scientific Reports Jun 2022The relationship between apolipoprotein B (APOB) and atrial fibrillation (AF) is less well-known. We aimed to investigate the association between APOB and AF by gender....
The relationship between apolipoprotein B (APOB) and atrial fibrillation (AF) is less well-known. We aimed to investigate the association between APOB and AF by gender. We conducted a case-control study including 1913 consecutive hospitalized patients to analyze the association between APOB and AF. 950 AF patients and 963 age-, sex-matched non-AF patients with sinus rhythm were evaluated. T-test, Mann-Whitney test, ANOVA, and Chi-square analysis were performed to analyze baseline data and intergroup comparisons. Pearson's correlation tests or Spearman correlation tests were performed to determine the interrelationships. Multiple regression analysis was performed to adjust for covariables. The receiver operator characteristic (ROC) curve was constructed to examine the performance of APOB. AF patients had lower APOB (P < 0.001) and an independent negative association between APOB and AF in both genders adjusting for confounding factors (OR 0.121, 95% CI 0.067-0.220, P < 0.001), regardless of statin use. APOB was positively correlated with total cholesterol (TC) (r = 0.529, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = 0.545, p < 0.001), apolipoprotein A1 (APOA1) (r = 0.083, p < 0.001), and albumin (ALB) (r = 0.134, p < 0.001). ROC curve analysis showed that APOB level = 0.895 g/L was the most optimal cut-off value, the area under the ROC curve was 0.722. This study shows a protective association of APOB with AF in men and women. It implies APOB may be a potential biomarker for AF with a promising cut-off point of 0.895 g/L and may involve initiating and maintaining AF along with several metabolic factors.
Topics: Apolipoprotein A-I; Apolipoprotein B-100; Apolipoproteins B; Atrial Fibrillation; Biomarkers; Case-Control Studies; Cholesterol, LDL; Female; Humans; Male
PubMed: 35688870
DOI: 10.1038/s41598-022-13773-2 -
Scientific Reports Feb 2022Apolipoproteins exert a key role on glucose metabolism; however, scarce data have examined the relationship between apolipoproteins and glycated haemoglobin (HbA1c) in... (Clinical Trial)
Clinical Trial
Apolipoproteins exert a key role on glucose metabolism; however, scarce data have examined the relationship between apolipoproteins and glycated haemoglobin (HbA1c) in Chinese adults. This study determined the cross-sectional and longitudinal associations of serum Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and the ApoB/A1 ratio with HbA1c in Chinese adults. A total of 1448 subjects (584 men and 864 women) aged 54.8 years were included in a baseline survey, and the concentrations of Apo and HbA1c were measured. A total of 826 participants were followed up approximately once after 3.94 ± 0.62 years. In cross-sectional analysis, serum ApoA1 was inversely associated with HbA1c, while ApoB and the ApoB/A1 ratio were positively associated with HbA1c. After further adjusting for the potential covariates, a higher ApoA1 was associated with lower HbA1c (Quartile 4 [Q4] vs. Q1 = 5.673% vs. 5.796%, P-trend = 0.014). In contrast, positive association of ApoB concentration and the ApoB/A1 ratio with HbA1c level were showed (Q4 vs. Q1 = 5.805% vs. 5.589% for ApoB; Q4 vs. Q1 = 5.841% vs. 5.582% for ApoB/A1 ratio). The longitudinal results showed no significant associations of ApoA1, ApoB levels and the ApoB/A1 ratio with HbA1c changes (all P-trends > 0.05). Path analysis suggested that body mass index did not have mediating effect on Apo-HbA1c association. Our findings revealed that higher ApoA1, lower ApoB concentrations and the ApoB/A1 ratio were associated with lower HbA1c level in Chinese adults.
Topics: Adult; Aged; Apolipoprotein A-I; Apolipoprotein B-100; Asian People; China; Female; Glycated Hemoglobin; Humans; Longitudinal Studies; Male; Middle Aged
PubMed: 35177752
DOI: 10.1038/s41598-022-06829-w