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Indian Heart Journal Mar 2024This review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and atherosclerosis, summarizes the existing evidence on Apo B as a... (Review)
Review
This review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and atherosclerosis, summarizes the existing evidence on Apo B as a predictor of atherosclerotic cardiovascular disease and recommendations of (inter)national treatment guidelines regarding Apo B in dyslipidemia management. A single Apo B molecule is present in every particle of very low-density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and lipoprotein(a). This unique single Apo B per particle ratio makes plasma Apo B concentration a direct measure of the number of circulating atherogenic lipoproteins. This review of global evidence on Apo B as a biomarker for atherosclerosis confirms that Apo B is a single atherogenic lipid marker present in all lipids sub-fractions except HDL-C, and thus, Apo B integrates and extends the information from triglycerides and cholesterol, which could simplify and improve care for atherosclerotic cardiovascular disease.
Topics: Humans; Apolipoproteins B; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Triglycerides
PubMed: 38599726
DOI: 10.1016/j.ihj.2023.12.001 -
Nature Genetics Feb 2023APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the...
APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the progression from normal to cancer cell and the APOBEC enzymes responsible. Here we whole-genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals and found that SBS2/SBS13 mutations were present in 17% of crypts, more frequent than most other normal tissues. Crypts with SBS2/SBS13 often had immediate crypt neighbors without SBS2/SBS13, suggesting that the underlying cause of SBS2/SBS13 is cell-intrinsic. APOBEC mutagenesis occurred in an episodic manner throughout the human lifespan, including in young children. APOBEC1 mRNA levels were very high in the small intestine epithelium, but low in the large intestine epithelium and other tissues. The results suggest that the high levels of SBS2/SBS13 in the small intestine are collateral damage from APOBEC1 fulfilling its physiological function of editing APOB mRNA.
Topics: Child; Humans; Child, Preschool; Apolipoproteins B; Cytidine Deaminase; Mutagenesis; RNA, Messenger; APOBEC-1 Deaminase; Intestine, Small
PubMed: 36702998
DOI: 10.1038/s41588-022-01296-5 -
Cardiovascular Drugs and Therapy Feb 2021Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists....
BACKGROUND
Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists. Specifically, new drugs are needed for non-responding or statin-intolerant subjects or patients considered at very high risk for cardiovascular events even though are already on treatment with the best standard of care.
RESULTS AND CONCLUSIONS
Besides, genetic and epidemiological studies and Mendelian randomization analyses have strengthened the linear correlation between the concentration of low-density lipoprotein cholesterol (LDL-C) and the incidence of cardiovascular events and highlighted various novel therapeutic targets. This review describes the novel strategies to reduce the levels of LDL-C, non-HDL-C, triglyceride, apolipoprotein B, and Lp(a), focusing on those developed using biotechnology-based strategies.
Topics: Antibodies, Monoclonal, Humanized; Apolipoproteins B; Cholesterol, LDL; Clinical Trials as Topic; Dyslipidemias; Genetic Therapy; Humans; Hypolipidemic Agents; Lysophospholipids; Oligonucleotides, Antisense; RNA, Small Interfering; Triglycerides
PubMed: 32519066
DOI: 10.1007/s10557-020-07017-6 -
Cardiovascular Therapeutics 2021Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in the regulation of LDL metabolism. There is evidence that circulating PCSK9 is a cardiovascular risk...
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in the regulation of LDL metabolism. There is evidence that circulating PCSK9 is a cardiovascular risk factor. In this study, we determined factors associated with circulating PCSK9 in a group of patients with type 2 diabetes mellitus (DM2). Material included 116 consecutive patients with DM2 from outpatient diabetes clinic. Circulating PCSK9, PTX3, apolipoprotein (apo) B100, apo B48, and apo C3 levels were determined by ELISA, apo A1 by immunoturbidimetry. The mean (sd) age of patients was 59.1 (11.1) years, the mean (sd) values of serum PCSK9 were 255.4 (106.97) ng/ml. Circulating PCSK9 correlated negatively with age ( = -0.21, < 0.05) and HbA1c ( = -0.21, < 0.05) and positively with BMI ( = 0.21, < 0.05), total cholesterol ( = 0.59), LDL-cholesterol ( = 0.50), triglyceride ( = 0.35), apo B100 ( = 0.43), apo A1 ( = 0.43) ( < 0.001 for all), apo C3 ( = 0.29, < 0.01), and apo B48 ( = 0.25, < 0.01) concentration and FLI ( = 0.26, < 0.01). Strong correlation between PTX3 and PCSK9 levels was observed ( = 0.47, < 0.001). Multiple stepwise backward regression analysis with PCSK9 as dependent variable revealed that PTX3, apo B100, apo A1, apo B48, and BMI were significantly positive and the presence of NAFLD and HbA1c negatively associated with PCSK9 concentrations. These variables together explain 57% of PCSK9 variability; the strongest relationship was observed between PCSK9 and PTX3 and apo B100. Our results indicate that circulating PCSK9 is significantly associated with inflammation marker PTX3 as well as atherogenic lipids and apolipoproteins C3, B100, and B48, which might be of value in understanding interactions between development of atherosclerosis and inflammatory state in DM2 patients.
Topics: Apolipoprotein A-I; Apolipoprotein C-III; Apolipoproteins B; C-Reactive Protein; Cholesterol, LDL; Diabetes Mellitus, Type 2; Humans; Middle Aged; Proprotein Convertase 9; Serum Amyloid P-Component
PubMed: 35024053
DOI: 10.1155/2021/7956161 -
Frontiers in Endocrinology 2023The correlation between dyslipidemia and periodontitis is revealed through epidemiological studies. However, the results are affected by several confounding factors....
INTRODUCTION
The correlation between dyslipidemia and periodontitis is revealed through epidemiological studies. However, the results are affected by several confounding factors. This study aims to elucidate the genetic causal association between circulating lipid traits and periodontitis by two-sample Mendelian randomization (MR) analysis.
METHODS
After the different screening processes, two cohorts of circulating lipid traits from the UK Biobank were used as exposure data, including five circulating lipid traits. The Periodontitis cohort was selected from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium as outcome data. In univariable MR, the inverse variance weighted (IVW) was used in conjunction with six additional analytical methods to assess causality. The Cochran Q test, I statistic, MR-PRESSO, and MR-Egger intercept were used to quantify heterogeneity and pleiotropy. The multivariable MR-IVW (MVMR-IVW) and MVMR-robust were mainly used as analytical methods in the multiple MR analyses.
RESULTS
The IVW estimates showed that genetically predicted Apolipoprotein A1 (apo A1) [odds ratio (OR)=1.158, 95% confidence interval (CI)=1.007-1.331, -value=0.040] was potentially associated with the risk of periodontitis, but the statistical power of the results was low. Multivariable MR analysis did not reveal any significant causal relationship between apo A1 and periodontitis (OR=0.72, 95% CI=0.36-1.41, -value=0.34). In the validation cohort, there was also no significant causal relationship between apo A1 and periodontitis (OR=1.079, 95% CI=0.903-1.290, -value=0.401). Meanwhile, genetically predicted Apolipoprotein B (apo B), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (all -values>0.05) were not significantly associated with the risk of periodontitis causal inference.
CONCLUSION
This MR analysis was unable to provide genetic evidence for the influence of these five circulating lipid traits on periodontitis. However, a more extensive study with a more comprehensive circulating lipid profile and periodontitis data is needed due to study limitations.
Topics: Humans; Apolipoprotein A-I; Mendelian Randomization Analysis; Apolipoproteins B; Cholesterol, HDL; Periodontitis
PubMed: 37583432
DOI: 10.3389/fendo.2023.1214232 -
Clinical Rheumatology Jun 2023Disturbed lipid metabolism was observed in systemic lupus erythematosus (SLE) patients. This study aimed to evaluate the relationships between dyslipidemia and visceral...
INTRODUCTION
Disturbed lipid metabolism was observed in systemic lupus erythematosus (SLE) patients. This study aimed to evaluate the relationships between dyslipidemia and visceral organ involvement, disease severity, inflammatory factors, and drug intake in SLE patients.
METHOD
Inpatients with SLE (n = 105) and healthy controls (HC) (n = 75) were recruited in this study. Clinical and laboratory data were collected from patient records. The concentrations of tumor necrosis factor receptors superfamily member1A (TNFRSF1A), member1B (TNFRSF1B) and adipokine angiopoietin-like 4 (ANGPTL4) in plasma were measured by ELISA.
RESULT
Compared to HC, serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and apolipoprotein B (ApoB) were significantly increased, while high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) were decreased in SLE patients. Patients with higher disease activity and renal damage suffered from more severe dyslipidemia. Renal functional parameters were closely correlated with serum lipid levels. Inflammatory factors were associated with dyslipidemia. The levels of TNFRSF1A and TNFRSF1B were obviously increased and associated with kidney involvement in SLE patients. Patients with high-dose glucocorticoid intake showed more severe dyslipidemia.
CONCLUSIONS
Attention should be paid to the dyslipidemia of SLE. Dyslipidemia is associated with inflammation and organ involvement in SLE. These findings might provide a new strategy for the treatment of SLE. Key Points • Serum levels of TG, TC, LDL, and ApoB were significantly increased, while HDL and ApoA1 were decreased in SLE patients. • Patients with higher disease activity and renal damage suffered from more severe dyslipidemia. Renal functional parameters and inflammatory factors were closely correlated with serum lipid levels. • Patients with high-dose glucocorticoid intake showed more severe dyslipidemia. • These findings might provide a new strategy for the treatment of SLE.
Topics: Humans; Glucocorticoids; Triglycerides; Lipoproteins, HDL; Inflammation; Lupus Erythematosus, Systemic; Dyslipidemias; Apolipoproteins B
PubMed: 36790644
DOI: 10.1007/s10067-023-06539-2 -
Cancer Medicine Nov 2023Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic...
BACKGROUND
Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic malignancy has been identified in population studies. However, it is still unclear if there is a relationship between cholesterol levels and plasma cell neoplasm in European ancestry.
METHODS
Prospective cohorts included 502,507 individuals from the UK Biobank who were followed up to 2019 and assessed total cholesterol(TC) levels, low-density lipoprotein (LDL) levels, high-density lipoprotein (HDL) levels, apolipoprotein A (ApoA) and apolipoprotein B (ApoB) as risk factors for plasma cell neoplasms with Cox proportional hazard regression and restricted cubic spline model. We also used two-sample Mendelian randomization to determine if the cholesterol level has a causal effect on developing plasma cell neoplasms.
RESULTS
We observed 1819 plasma cell neoplasm cases during 14.2 years of follow-up in the UK Biobank. We found higher blood serum cholesterol levels at baseline were associated with a lower risk of plasma cell neoplasm in our study. All lipid profiles we analyzed in this study were inversely associated with plasma cell neoplasm risk (all p <0.005) but triglycerides did not have such association. However, there was no suggestive association of genetically predicted serum LDL, HDL, and total cholesterol levels with multiple myeloma.
CONCLUSION
Low serum total cholesterol, LDL, HDL, ApoA, and ApoB levels were all associated with increasing the risk of plasma cell neoplasm.
Topics: Humans; Aged; Cohort Studies; Prospective Studies; Multiple Myeloma; Biological Specimen Banks; Cholesterol, HDL; Cholesterol, LDL; Apolipoproteins B; Risk Factors; Triglycerides; Apolipoproteins A
PubMed: 37908181
DOI: 10.1002/cam4.6649 -
Pharmacological Research Sep 2023The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and...
The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and clinical evidence strongly supports the concept that the lipid content of the particles is secondary to the number of circulating atherogenic particles that are trapped within the arterial lumen. Since each low-density lipoproteins (LDL) particle contains one apoB molecule, as do intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, apoB level represents the total number of atherogenic lipoproteins, which is independent of particle density, and not affected by the heterogeneity of particle cholesterol content (clinically evaluated by LDL-cholesterol level). From this perspective, apoB is proposed as a better proxy to LDL-cholesterol for assessing atherosclerotic cardiovascular disease risk, especially in specific subgroups of patients, including subjects with diabetes mellitus, with multiple cardiometabolic risk factors (obesity, metabolic syndrome, insulin resistance, and hypertension) and with high triglyceride levels and very low LDL-cholesterol levels. Therefore, given the causal role of LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) development, routine measurement of both LDL-cholesterol and apoB is of utmost importance to properly estimate global cardiovascular risk and to determine the 'residual' risk of ASCVD in patients receiving therapy, as well as to monitor therapeutic effectiveness.
Topics: Humans; Apolipoproteins B; Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Risk Assessment; Triglycerides
PubMed: 37517561
DOI: 10.1016/j.phrs.2023.106873 -
ELife May 2023Extracellular vesicles (EVs) are released by all cells into biofluids such as plasma. The separation of EVs from highly abundant free proteins and similarly sized...
Extracellular vesicles (EVs) are released by all cells into biofluids such as plasma. The separation of EVs from highly abundant free proteins and similarly sized lipoproteins remains technically challenging. We developed a digital ELISA assay based on Single Molecule Array (Simoa) technology for ApoB-100, the protein component of several lipoproteins. Combining this ApoB-100 assay with previously developed Simoa assays for albumin and three tetraspanin proteins found on EVs (Ter-Ovanesyan, Norman et al., 2021), we were able to measure the separation of EVs from both lipoproteins and free proteins. We used these five assays to compare EV separation from lipoproteins using size exclusion chromatography with resins containing different pore sizes. We also developed improved methods for EV isolation based on combining several types of chromatography resins in the same column. We present a simple approach to quantitatively measure the main impurities of EV isolation in plasma and apply this approach to develop novel methods for enriching EVs from human plasma. These methods will enable applications where high-purity EVs are required to both understand EV biology and profile EVs for biomarker discovery.
Topics: Humans; Apolipoprotein B-100; Lipoproteins; Extracellular Vesicles; Chromatography, Gel; Enzyme-Linked Immunosorbent Assay
PubMed: 37252755
DOI: 10.7554/eLife.86394 -
BMC Endocrine Disorders Apr 2021Apolipoprotein (Apo) may be associated with type 2 diabetes (T2D), however, little is known whether or not serum apolipoproteins are correlated with fasting blood...
BACKGROUND
Apolipoprotein (Apo) may be associated with type 2 diabetes (T2D), however, little is known whether or not serum apolipoproteins are correlated with fasting blood glucose (FBG) and the prevalence of T2D in Chinese populations. In this study, we examined the association of serum ApoA1, ApoB, and the ratio of ApoB/ApoA1 (ApoB/A1 ratio) with T2D and FBG level, and compared apolipoprotein indicators in predicting T2D in Chinese adults.
METHODS
A total of 1027 subjects were enrolled in this cross-sectional study. The association of ApoA1, ApoB, and ApoB/A1 ratio with T2D prevalence was determined using logistic regression models. Multivariate-analysis of covariance (ANCOVA) was performed for comparisons of the mean difference in FBG level.
RESULTS
We found that ApoB and ApoB/A1 ratio were positively associated with T2D prevalence and FBG, while inverse association was noted between ApoA1 and T2D prevalence as well as FBG. Stratified analyses for sex, age, body mass index (BMI), smoking, and alcohol consumption showed no significant difference for the association of ApoA1, ApoB, and ApoB/A1 ratio with the prevalence of T2D among subgroups (all p-interactions> 0.05). Nonetheless, ApoA1 poorly performed in predicting T2D as it provided an AUC value of 0.310 that was significantly lower than those observed for ApoB (AUC value: 0.631) and ApoB/A1 ratio (AUC value: 0.685). Finally, path analyses indicated that the association between ApoB and T2D was mediated by BMI.
CONCLUSIONS
This study reveals the association of serum ApoA1, ApoB, and ApoB/A1 ratio with T2D and FBG in Chinese adults, suggesting that ApoB and ApoB/A1 ratio may be early indicators for predicting T2D. Prospective investigation in large cohort is needed.
Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; Asian People; Blood Glucose; Body Mass Index; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Prevalence
PubMed: 33794863
DOI: 10.1186/s12902-021-00726-5