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Current Opinion in Lipidology Oct 2021Lipid-mediated atherogenesis is hallmarked by a chronic inflammatory state. Low-density lipoprotein cholesterol (LDL-C), triglyceride rich lipoproteins (TRLs), and... (Review)
Review
PURPOSE OF REVIEW
Lipid-mediated atherogenesis is hallmarked by a chronic inflammatory state. Low-density lipoprotein cholesterol (LDL-C), triglyceride rich lipoproteins (TRLs), and lipoprotein(a) [Lp(a)] are causally related to atherosclerosis. Within the paradigm of endothelial activation and subendothelial lipid deposition, these lipoproteins induce numerous pro-inflammatory pathways. In this review, we will outline the effects of lipoproteins on systemic inflammatory pathways in atherosclerosis.
RECENT FINDINGS
Apolipoprotein B-containing lipoproteins exert a variety of pro-inflammatory effects, ranging from the local artery to systemic immune cell activation. LDL-C, TRLs, and Lp(a) induce endothelial dysfunction with concomitant activation of circulating monocytes through enhanced lipid accumulation. The process of trained immunity of the innate immune system, predominantly induced by LDL-C particles, hallmarks the propagation of the low-grade inflammatory response. In concert, bone marrow activation induces myeloid skewing, further contributing to immune cell mobilization and plaque progression.
SUMMARY
Lipoproteins and inflammation are intertwined in atherogenesis. Elucidating the inflammatory pathways will provide new opportunities for therapeutic agents.
Topics: Apolipoproteins B; Atherosclerosis; Endothelium; Humans; Inflammation; Monocytes
PubMed: 34392272
DOI: 10.1097/MOL.0000000000000779 -
Revista de Investigacion Clinica;... 2018Familial combined hyperlipidemia (FCHL) is the most prevalent primary dyslipidemia; however, it frequently remains undiagnosed and its precise definition is a subject of... (Review)
Review
Familial combined hyperlipidemia (FCHL) is the most prevalent primary dyslipidemia; however, it frequently remains undiagnosed and its precise definition is a subject of controversy. FCHL is characterized by fluctuations in serum lipid concentrations and may present as mixed hyperlipidemia, isolated hypercholesterolemia, hypertriglyceridemia, or as a normal serum lipid profile in combination with abnormally elevated levels of apolipoprotein B. FCHL is an oligogenic primary lipid disorder, which can occur due to the interaction of several contributing variants and mutations along with environmental triggers. Controversies surrounding the relevance of identifying FCHL as a cause of isolated hypertriglyceridemia and a differential diagnosis of familial hypertriglyceridemia are offset by the description of associations with USF1 and other genetic traits that are unique for FCHL and that are shared with other conditions with similar pathophysiological mechanisms. Patients with FCHL are at an increased risk of cardiovascular disease and mortality and have a high frequency of comorbidity with other metabolic conditions such as type 2 diabetes, non-alcoholic fatty liver disease, steatohepatitis, and the metabolic syndrome. Management usually requires lipid-lowering therapy directed toward reducing cholesterol and triglyceride concentrations along with cardiovascular risk protection. In recent years, the number of research studies on FCHL has been decreasing, mainly due to a lack of recognition of its impact on disease burden and comorbidity and the complexity in identifying probands for studies. This creates areas of opportunity to develop research for FCHL in epidemiology, genetics, pathophysiology, therapeutics, and cardiovascular risk management, which are discussed in depth in this review. (REV INVEST CLIN. 2018;70:224-36).
Topics: Animals; Apolipoproteins B; Cardiovascular Diseases; Diagnosis, Differential; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type IV; Lipids; Risk Factors
PubMed: 30307446
DOI: 10.24875/RIC.18002575 -
Current Opinion in Lipidology Feb 2017Abdominal obesity is associated with a number of important metabolic abnormalities including liver steatosis, insulin resistance and an atherogenic lipoprotein profile... (Review)
Review
PURPOSE OF REVIEW
Abdominal obesity is associated with a number of important metabolic abnormalities including liver steatosis, insulin resistance and an atherogenic lipoprotein profile (termed dyslipidemia). The purpose of this review is to highlight recent progress in understanding the pathogenesis of this dyslipidemia.
RECENT FINDINGS
Recent results from kinetic studies using stable isotopes indicate that the hypertriglyceridemia associated with abdominal obesity stems from dual mechanisms: (1) enhanced secretion of triglyceride-rich lipoproteins and (2) impaired clearance of these lipoproteins. The over-secretion of large triglyceride-rich VLDLs from the liver is linked to hepatic steatosis and increased visceral adiposity. The impaired clearance of triglyceride-rich lipoproteins is linked to increased levels of apolipoprotein C-III, a key regulator of triglyceride metabolism.
SUMMARY
Elucidation of the pathogenesis of the atherogenic dyslipidemia in abdominal obesity combined with the development of novel treatments based on apolipoprotein C-III may in the future lead to better prevention, diagnosis and treatment of the atherogenic dyslipidemia in abdominal obesity.
Topics: Animals; Apolipoproteins B; Dyslipidemias; Humans; Kinetics; Liver; Obesity, Abdominal; Triglycerides
PubMed: 27898581
DOI: 10.1097/MOL.0000000000000375 -
Multiple Sclerosis and Related Disorders Jan 2016Multiple sclerosis (MS) is a chronic central nervous system disease that is associated with progressive loss of myelin and subsequent axonal degeneration. Cholesterol is... (Review)
Review
Multiple sclerosis (MS) is a chronic central nervous system disease that is associated with progressive loss of myelin and subsequent axonal degeneration. Cholesterol is an essential component of mammalian cellular and myelin membranes. In this systematic review, we examined the relationship between levels of cholesterol and markers of cholesterol turnover in circulation and/or cerebrospinal fluid (CSF) and disease outcomes in adults with clinically isolated syndrome (CIS) or confirmed MS. Studies suggest that elevated levels of circulating low density lipoprotein cholesterol (LDL), total cholesterol, and particularly, apolipoprotein B and oxidized LDL are associated with adverse clinical and MRI outcomes in MS. These relationships were observed as early as CIS. The studies also suggest that oxysterols, cholesterol precursors, and apolipoprotein E may be markers of specific disease processes in MS, but more research is required to elucidate these processes and relationships. Taken together, the data indicate that cholesterol and markers of cholesterol turnover have potential to be used clinically as biomarkers of disease activity and may even be implicated in the pathogenesis of MS.
Topics: Apolipoproteins; Apolipoproteins B; Biomarkers; Cholesterol; Cholesterol, LDL; Humans; Multiple Sclerosis
PubMed: 26856944
DOI: 10.1016/j.msard.2015.10.005 -
Scientific Reports May 2023In view of the current debate about the relationship between lipids and deep venous thrombosis (DVT) in clinical studies, a two-sample Mendelian randomization (MR) study...
In view of the current debate about the relationship between lipids and deep venous thrombosis (DVT) in clinical studies, a two-sample Mendelian randomization (MR) study was conducted to clarify the effects of five circulating lipids (apolipoprotein A1, apolipoprotein B, low-density lipoprotein, high-density lipoprotein and triglycerides) on DVT from the perspective of genetic inheritance. Five lipids (exposure) were analysed by MR with DVT (outcome) from two different data sources. For the analysis, we used inverse variance weighting and a weighted mode, weighted median, simple mode and MR-Egger regression to analyse the effect of circulating lipids on DVT. In addition, we used the MR-Egger intercept test, Cochran's Q test and "leave-one-out" sensitivity analysis to evaluate horizontal multiplicity, heterogeneity and stability, respectively, in the analysis. In the analysis, the two-sample Mendelian randomization analysis of five common circulating lipids and DVT showed that common circulating lipids had no causal effect on DVT, which is somewhat inconsistent with the findings of many published observational studies. Based on our results, our two-sample MR analysis failed to detect a statistically significant causal relationship between five common circulating lipids and DVT.
Topics: Humans; Mendelian Randomization Analysis; Apolipoproteins B; Lipoproteins, HDL; Lipoproteins, LDL; Venous Thrombosis; Genome-Wide Association Study
PubMed: 37156934
DOI: 10.1038/s41598-023-34726-3 -
Journal of Lipid Research Jul 2018Triglycerides are the conventional tool to measure VLDLs, whereas LDL cholesterol (LDL-C) is the conventional tool to measure LDLs. Multiple epidemiological studies,... (Review)
Review
Triglycerides are the conventional tool to measure VLDLs, whereas LDL cholesterol (LDL-C) is the conventional tool to measure LDLs. Multiple epidemiological studies, including a series of genetically based analyses, have demonstrated that cardiovascular risk is related to triglycerides independently of LDL-C, and this has led to a series of new therapeutic agents designed specifically to reduce plasma triglycerides. The triglyceride hypothesis posits that increased levels of triglycerides increase cardiovascular risk and decreasing plasma triglycerides decreases cardiovascular risk. In this work, we will examine the validity of the triglyceride hypothesis by detailing the biological complexities associated with hypertriglyceridemia, the genetic epidemiological evidence in favor of hypertriglyceridemia, the evidence from the fibrate randomized clinical trials relating triglycerides and clinical outcomes, and the completeness of the evidence from the initial studies of novel mutations and the therapeutic agents based on these mutations that lower triglycerides. Because of the multiple metabolic links between VLDL and LDL, we will try to demonstrate that measuring triglycerides and LDL-C alone are inadequate to document the lipoprotein profile. We will try to demonstrate that apoB must be measured, as well as triglycerides and cholesterol, to have an accurate estimate of lipoprotein status.
Topics: Apolipoproteins B; Cardiovascular Diseases; Humans; Hypertriglyceridemia; Lipoproteins; Risk Factors
PubMed: 29769239
DOI: 10.1194/jlr.R082271 -
Environment International Jan 2024Per- and polyfluoroalkyl substances (PFAS) can disrupt liver homeostasis. Studies have shown that a single exposure to PFAS may provoke abnormal liver function; however,...
Per- and polyfluoroalkyl substances (PFAS) can disrupt liver homeostasis. Studies have shown that a single exposure to PFAS may provoke abnormal liver function; however, few studies have investigated the overall effect of PFAS mixtures. We aimed to investigate associations between exposure to PFAS mixtures and liver function indices and explore the relevant mechanisms. This study included 278 adult males from Guangzhou, China. Serum metabolite profiles were analyzed using untargeted metabolomics. We applied weighted quantile sum (WQS) regression as well as Bayesian kernel machine regression (BKMR) to analyze the association of nine PFAS mixtures with 14 liver function indices. PFAS mixtures were positively associated with apolipoprotein B (APOB) and gamma-glutamyltransferase (GGT) and negatively associated with direct bilirubin (DBIL) and total bilirubin (TBIL) in both the WQS and BKMR analyses. In addition, Spearman's correlation test showed individual PFAS correlated with APOB, GGT, TBIL, and DBIL, while there's little correlation between individual PFAS and other liver function indices. In linear regression analysis, PFHxS, PFOS, PFHpS, PFNA, PFDA, and PFUdA were associated with APOB; PFOA, PFDA, PFOS, PFNA, and PFUdA were associated with GGT. Subsequently, a metabolome-wide association study and mediation analysis were combined to explore metabolites that mediate these associations. The mechanisms linking PFAS to APOB and GGT are mainly related with amino acid and glycerophospholipid metabolism. High-dimensional mediation analysis showed that glycerophospholipids are the main markers of the association between PFAS and APOB, and that (R)-dihydromaleimide, Ile Leu, (R)-(+)-2-pyrrolidone-5-carboxylic acid, and L-glutamate are the main markers of the association between PFAS and GGT. In summary, overall associations between PFAS and specific indices of liver function were found using two statistical methods; the metabolic pathways and markers identified here may serve to prompt more detailed study in animal-based systems, as well as a similar detailed analysis in other populations.
Topics: Animals; Male; Bayes Theorem; Apolipoproteins B; Bilirubin; Liver; Fluorocarbons; Environmental Pollutants; Alkanesulfonic Acids
PubMed: 38163401
DOI: 10.1016/j.envint.2023.108405 -
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 -
Global Heart Jan 2021Apolipoprotein B (apoB) integrates and extends the information from the conventional measures of atherogenic cholesterol and triglyceride. To illustrate how apoB could...
BACKGROUND AND AIMS
Apolipoprotein B (apoB) integrates and extends the information from the conventional measures of atherogenic cholesterol and triglyceride. To illustrate how apoB could simplify and improve the management of dyslipoproteinemia, we compared conventional lipid markers and apoB in a sample of Americans and Asian Indians.
METHODS
Data from the US National Health and Nutrition Examination Survey (NHANES) (11,778 participants, 2009-2010, 2011-2012), and the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) cohort study in Delhi, India (4244 participants), 2011 were evaluated. We compared means and distributions of plasma lipids, and apo B using the Mann-Whitney U test and Fisher's exact test. A p value of < 0.05 was considered significant.
RESULTS
The plasma lipid profile differed between Asian Indians and Americans. Plasma triglycerides were greater, but HDL-C lower in Asian Indians than in Americans. By contrast, total cholesterol, non-HDL-C, and LDL-C were all significantly higher in Americans than Asian Indians. However, apoB was significantly higher in Asian Indians than Americans. The LDL-C/apoB ratio and the non-HDL-C/apoB ratio were both significantly lower in Asian Indians than Americans.
CONCLUSION
Whether Americans or Asian Indians are at higher risk from apoB lipoproteins cannot be determined based on their lipid levels because the information from lipids cannot be integrated. ApoB, however, integrates and extends the information from triglycerides and cholesterol. Replacing the conventional lipid panel with apoB for routine follow ups could simultaneously simplify and improve clinical care.
Topics: Apolipoproteins B; Cholesterol, HDL; Cohort Studies; Humans; Lipids; Nutrition Surveys; Triglycerides
PubMed: 33598387
DOI: 10.5334/gh.882 -
Nutrients Jan 2023In the present review, we provide a comprehensive narrative overview of the current knowledge on the effects of total and specific types of nut consumption (excluding... (Review)
Review
In the present review, we provide a comprehensive narrative overview of the current knowledge on the effects of total and specific types of nut consumption (excluding nut oil) on blood lipids and lipoproteins. We identified a total of 19 systematic reviews and meta-analyses of randomized controlled trials (RCTs) that were available in PubMed from the inception date to November 2022. A consistent beneficial effect of most nuts, namely total nuts and tree nuts, including walnuts, almonds, cashews, peanuts, and pistachios, has been reported across meta-analyses in decreasing total cholesterol (mean difference, MD, -0.09 to -0.28 mmol/L), LDL-cholesterol (MD, -0.09 to -0.26 mmol/L), and triglycerides (MD, -0.05 to -0.17 mmol/L). However, no effects on HDL-cholesterol have been uncovered. Preliminary evidence indicates that adding nuts into the regular diet reduces blood levels of apolipoprotein B and improves HDL function. There is also evidence that nuts dose-dependently improve lipids and lipoproteins. Sex, age, or nut processing are not effect modifiers, while a lower BMI and higher baseline lipid concentrations enhance blood lipid/lipoprotein responses. While research is still emerging, the evidence thus far indicates that nut-enriched diets are associated with a reduced number of total LDL particles and small, dense LDL particles. In conclusion, evidence from clinical trials has shown that the consumption of total and specific nuts improves blood lipid profiles by multiple mechanisms. Future directions in this field should include more lipoprotein particle, apolipoprotein B, and HDL function studies.
Topics: Nuts; Lipids; Cholesterol, LDL; Lipoproteins; Apolipoproteins B
PubMed: 36771303
DOI: 10.3390/nu15030596