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Scientific Reports May 2024Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in...
Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC < middle-stage HCC < advanced-stage HCC, Class A LC < Class B LC < Class C LC. Serum ApoB/ApoA1 ratio combined diagnosis with AFP exhibited the capability of increasing the detection efficacy and specificity of AFP for HCC and AFP-negative HCC. The incidence of LC and HCC in the respective logistic regression model showed a negative correlation with the serum ApoB/ApoA1 ratio in CHB patients (P < 0.05). After all confounding factors covered in this study were regulated, the result of the restricted cubic spline analysis suggested that in a certain range, serum ApoB/ApoA1 ratio showed an inverse correlation with the prevalence of LC or HCC in CHB patients. Serum ApoB/ApoA1 ratio in CHB patients may be conducive to identifying high-risk patients for HCC or LC, such that LC and HCC can be early diagnosed and treated.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Apolipoprotein A-I; Male; Female; Middle Aged; Liver Cirrhosis; Hepatitis B, Chronic; Adult; Apolipoprotein B-100; Hepatitis B virus; ROC Curve; Case-Control Studies; Apolipoproteins B
PubMed: 38744926
DOI: 10.1038/s41598-024-61820-x -
Obesity Surgery Jul 2024Metabolic and Bariatric surgery (MBS) leads to significant weight loss and improvements in obesity-related comorbidities. However, the impact of MBS on Apolipoprotein...
BACKGROUND
Metabolic and Bariatric surgery (MBS) leads to significant weight loss and improvements in obesity-related comorbidities. However, the impact of MBS on Apolipoprotein B100 (Apo-B100) regulation is unclear. Apo-B100 is essential for the assembly and secretion of serum lipoprotein particles. Elevated levels of these factors can accelerate the development of atherosclerotic plaques in blood vessels. This study aimed to evaluate changes in Apo-B100 levels following MBS.
METHODS
121 participants from the Iranian National Obesity and Metabolic Surgery Database (INOSD) underwent Laparoscopic Sleeve Gastrectomy (LSG) (n = 43), One-Anastomosis Gastric Bypass (OAGB) (n = 70) or Roux-en-Y Gastric Bypass (RYGB) (n = 8). Serum Apo-B100, lipid profiles, liver enzymes, and fasting glucose were measured preoperatively and six months postoperatively.
RESULTS
Apo-B100 levels significantly decreased from 94.63 ± 14.35 mg/dL preoperatively to 62.97 ± 19.97 mg/dL after six months (p < 0.01), alongside reductions in total cholesterol, triglycerides, LDL, VLDL, AST, and ALT (p < 0.05). Greater Apo-B100 reductions occurred in non-diabetics versus people with diabetes (p = 0.012) and strongly correlated with baseline Apo-B100 (r = 0.455, p < 0.01) and LDL levels (r = 0.413, p < 0.01). However, surgery type did not impact Apo-B100 changes in multivariate analysis (p > 0.05).
CONCLUSION
Bariatric surgery leads to a significant reduction in Apo-B100 levels and improvements in lipid profiles and liver enzymes, indicating a positive impact on dyslipidemia and cardiovascular risk in individuals with high BMI.
Topics: Humans; Female; Apolipoprotein B-100; Male; Prospective Studies; Adult; Obesity, Morbid; Body Mass Index; Middle Aged; Bariatric Surgery; Weight Loss; Gastrectomy; Gastric Bypass; Iran; Laparoscopy; Treatment Outcome
PubMed: 38744799
DOI: 10.1007/s11695-024-07258-6 -
Scientific Reports May 2024Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of... (Observational Study)
Observational Study
Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of lipoprotein subspecies in CVDs. In this study, we comprehensively investigated several lipoproteins and their subspecies, as well as other metabolites, in relation to coronary heart disease (CHD), heart failure (HF) and ischemic stroke (IS) longitudinally and by Mendelian randomization (MR) leveraging NMR-measured metabolomic data from 118,012 UK Biobank participants. We found that 123, 110 and 36 analytes were longitudinally associated with myocardial infarction, HF and IS (FDR < 0.05), respectively, and 25 of those were associated with all three outcomes. MR analysis suggested that genetically predicted levels of 70, 58 and 7 analytes were associated with CHD, HF and IS (FDR < 0.05), respectively. Two analytes, ApoB/ApoA1 and M-HDL-C were associated with all three CVD outcomes in the MR analyses, and the results for M-HDL-C were concordant in both observational and MR analyses. Our results implied that the apoB/apoA1 ratio and cholesterol in medium size HDL were particularly of importance to understand the shared pathophysiology of CHD, HF and IS and thus should be further investigated for the prevention of all three CVDs.
Topics: Humans; Mendelian Randomization Analysis; Cardiovascular Diseases; Male; Female; Risk Factors; Middle Aged; Magnetic Resonance Spectroscopy; Apolipoprotein A-I; Aged; Cholesterol, HDL; Coronary Disease; Metabolomics; Apolipoprotein B-100; Ischemic Stroke; Heart Failure
PubMed: 38724583
DOI: 10.1038/s41598-024-61440-5 -
Lipids in Health and Disease May 2024Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with... (Observational Study)
Observational Study
BACKGROUND
Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited.
METHODS
This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment.
RESULTS
Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions.
CONCLUSION
Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.
Topics: Humans; Male; Female; Middle Aged; Prospective Studies; Aged; Triglycerides; Risk Factors; Cholesterol, LDL; Lipoprotein(a); Cholesterol; Hypolipidemic Agents; Apolipoproteins B; Cardiovascular Diseases; Cholesterol, HDL; Biomarkers
PubMed: 38715079
DOI: 10.1186/s12944-024-02078-0 -
The Journal of International Medical... May 2024To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with...
OBJECTIVE
To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD).
METHODS
This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis.
RESULTS
A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients.
CONCLUSION
KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.
Topics: Humans; Mucocutaneous Lymph Node Syndrome; Immunoglobulins, Intravenous; Male; Female; Coronary Artery Disease; Child, Preschool; Retrospective Studies; Infant; Cholesterol, LDL; Drug Resistance; Lipids; Child; Coronary Vessels; Risk Factors; Apolipoproteins B; Prognosis
PubMed: 38713460
DOI: 10.1177/03000605241252115 -
Journal of Molecular Biology Dec 2023Cytidine (C) to Uridine (U) RNA editing is a post-transcription modification that is involved in diverse biological processes. APOBEC1 (A1) catalyzes the conversion of...
Cytidine (C) to Uridine (U) RNA editing is a post-transcription modification that is involved in diverse biological processes. APOBEC1 (A1) catalyzes the conversion of C-to-U in RNA, which is important in regulating cholesterol metabolism through its editing activity on ApoB mRNA. However, A1 requires a cofactor to form an "editosome" for RNA editing activity. A1CF and RBM47, both RNA-binding proteins, have been identified as cofactors that pair with A1 to form editosomes and edit ApoB mRNA and other cellular RNAs. SYNCRIP is another RNA-binding protein that has been reported as a potential regulator of A1, although it is not directly involved in A1 RNA editing activity. Here, we describe the identification and characterization of a novel cofactor, RBM46 (RNA-Binding-Motif-protein-46), that can facilitate A1 to perform C-to-U editing on ApoB mRNA. Additionally, using the low-error circular RNA sequencing technique, we identified novel cellular RNA targets for the A1/RBM46 editosome. Our findings provide further insight into the complex regulatory network of RNA editing and the potential new function of A1 with its cofactors.
Topics: Humans; APOBEC-1 Deaminase; Apolipoproteins B; Cytidine; HEK293 Cells; RNA Editing; RNA, Messenger; RNA-Binding Proteins; Uridine
PubMed: 38708190
DOI: 10.1016/j.jmb.2023.168333 -
ACS Applied Materials & Interfaces May 2024Atherosclerosis is the main risk factor for cardiovascular disease, which accounts for the majority of mortality worldwide. A significantly increased plasma level of...
Atherosclerosis is the main risk factor for cardiovascular disease, which accounts for the majority of mortality worldwide. A significantly increased plasma level of low-density lipoprotein cholesterol (LDL-C), surrounded by a monolayer of phospholipids, free cholesterol, and one apolipoprotein B-100 (ApoB-100) in the blood, plays the most significant role in driving the development of atherosclerosis. Commercially available cholesterol-lowering drugs are not sufficient for preventing recurrent cardiovascular events. Developing alternative strategies to decrease the plasma cholesterol levels is desirable. Herein, we develop an approach for reducing LDL-C levels using gas-filled microbubbles (MBs) that were coated with anti-ApoB100 antibodies. These targeted MB could selectively capture LDL particles in the bloodstream through forming LDL-MB complexes and transport them to the liver for degradation. Further immunofluorescence staining and lipidomic analyses showed that these LDL-MB complexes may be taken up by Kupffer cells and delivered to liver cells and bile acids, greatly inhibiting atherosclerotic plaque growth. More importantly, ultrasound irradiation of these LDL-MB complexes that accumulated in the liver may induce acoustic cavitation effects, significantly enhancing the delivery of LDL into liver cells and accelerating their degradation. Our study provides a strategy for decreasing LDL-C levels and inhibiting the progression of atherosclerosis.
Topics: Microbubbles; Apolipoprotein B-100; Animals; Liver; Plaque, Atherosclerotic; Mice; Lipoproteins, LDL; Humans; Male; Mice, Inbred C57BL; Atherosclerosis
PubMed: 38700017
DOI: 10.1021/acsami.4c00999 -
Arteriosclerosis, Thrombosis, and... Jun 2024LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL (high-density lipoprotein) into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesteryl ester-enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport.
METHODS
We conducted a randomized, placebocontrolled, crossover study in 5 volunteers with atherosclerotic cardiovascular disease, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration (300-mg loading dose followed by 150 mg at 48 hours) on the in vivo metabolism of HDL APO (apolipoprotein)A1 and APOA2, and the APOB100-lipoproteins, very low density, intermediate density, and low-density lipoproteins.
RESULTS
As expected, recombinant human LCAT treatment significantly increased HDL-cholesterol (34.9 mg/dL; ≤0.001), and this was mostly due to the increase in cholesteryl ester content (33.0 mg/dL; =0.014). This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. There were also no significant changes in the metabolism of APOB100-lipoproteins.
CONCLUSIONS
Our results suggest that an acute increase in LCAT activity drives greater flux of cholesteryl ester through the reverse cholesterol transport pathway without significantly altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.
Topics: Humans; Phosphatidylcholine-Sterol O-Acyltransferase; Recombinant Proteins; Cross-Over Studies; Male; Apolipoprotein A-I; Middle Aged; Cholesterol, HDL; Apolipoprotein A-II; Female; Cholesterol Esters; Atherosclerosis; Apolipoprotein B-100; Aged; Adult; Lipoproteins
PubMed: 38695168
DOI: 10.1161/ATVBAHA.123.320387 -
European Journal of Pharmacology Aug 2024Sodium-glucose cotransporter 2 (SGLT2) inhibitors offer a novel therapeutic avenue for myocardial infarction (MI). However, the exact nature of this relationship and the... (Meta-Analysis)
Meta-Analysis
AIMS
Sodium-glucose cotransporter 2 (SGLT2) inhibitors offer a novel therapeutic avenue for myocardial infarction (MI). However, the exact nature of this relationship and the underlying mechanisms are not fully understood.
METHODS
Utilizing a two-sample Mendelian Randomization (MR) analysis, we elucidated the causal effects stemming from the inhibition of SGLT2 on MI. Then, The pool of 4907 circulating proteins within the plasma proteome were utilized to explore the mediators of SGLT2 inhibitors on MI. Protein-protein network and enrichment analysis were conducted to clarify the potential mechanism. Finally, employing MR analysis and meta-analysis techniques, we systematically assessed the causal associations between SGLT2 inhibition and coronary heart diseases (CHD).
RESULTS
SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of MI (odds ratio [OR] = 0.462, [95% CI 0.222, 0.958], P = 0.038). Among 4907 circulating proteins, we identified APOB and CCL17 which were related to both SGLT2 inhibition and MI. Mediation analysis showed evidence of the indirect effect of SGLT2 inhibition on MI through APOB (β = -0.557, 95%CI [-1.098, -0.155]) with a mediated proportion of 72%, and CCL17 (β = -0.176, 95%CI [-0.332, -0.056]) with a mediated proportion of 17%. The meta-analysis result showed that SGLT2 inhibition was associated with a lower risk of CHD.
CONCLUSION
Based on proteome-wide mendelian randomization, APOB and CCL17 were seen as mediators in the protective effect of SGLT2 inhibition against myocardial infarction.
Topics: Mendelian Randomization Analysis; Myocardial Infarction; Humans; Sodium-Glucose Transporter 2 Inhibitors; Proteome; Apolipoproteins B
PubMed: 38679119
DOI: 10.1016/j.ejphar.2024.176619 -
Atherosclerosis Jun 2024The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial.
METHODS
Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT.
RESULTS
In the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (-0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94-0.99) for a -7 mg/dL (-0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01-1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01-1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96-1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91-1.15) in the PROMINENT trial.
CONCLUSIONS
Absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm.
Topics: Humans; Cholesterol, LDL; Female; Male; Middle Aged; Cholesterol; Aged; Triglycerides; Treatment Outcome; Denmark; Biomarkers; Apolipoprotein B-100; Cardiovascular Diseases; Atherosclerosis; Apolipoproteins B; Adult; Hypolipidemic Agents; Benzoxazoles; Butyrates; Lipoproteins
PubMed: 38678642
DOI: 10.1016/j.atherosclerosis.2024.117556