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The American Journal of Clinical... Jul 2018
Topics: Apolipoprotein A-I; Apolipoprotein A-II; Epigenomics; Humans; Lipid Metabolism; Metabolomics; Obesity
PubMed: 29982311
DOI: 10.1093/ajcn/nqy136 -
Clinica Chimica Acta; International... Apr 2020Dyslipidemia, characterized by increased plasma levels of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglyceride... (Review)
Review
Dyslipidemia, characterized by increased plasma levels of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglyceride (TG), and reduced plasma levels of high-density lipoprotein cholesterol (HDL-C), is confirmed as a hallmark of obesity and cardiovascular diseases (CVD), posing serious risks to the future health of humans. Thus, it is important to understand the molecular metabolism of dyslipidemia, which could help reduce the morbidity and mortality of obesity and CVD. Currently, several exchangeable apolipoproteins, such as apolipoprotein A1 (ApoA1), apolipoprotein A5 (ApoA5), apolipoprotein E (ApoE), and apolipoprotein C3 (ApoC3), have been verified to exert vital effects on modulating lipid metabolism and homeostasis both in plasma and in cells, which consequently affect dyslipidemia. In the present review, we summarize the findings of the effect of exchangeable apolipoproteins on affecting lipid metabolism in adipocytes and hepatocytes. Furthermore, we also provide new insights into the mechanisms by which the exchangeable apolipoproteins influence the pathogenesis of dyslipidemia and its related cardio-metabolic disorders.
Topics: Adipocytes; Apolipoprotein A-I; Apolipoprotein A-V; Apolipoprotein C-III; Apolipoproteins; Apolipoproteins E; Cardiovascular Diseases; Dyslipidemias; Female; Hepatocytes; Humans; Lipid Metabolism; Male; Obesity
PubMed: 31981585
DOI: 10.1016/j.cca.2020.01.015 -
Prostaglandins & Other Lipid Mediators Nov 2018Apolipoprotein A-IV is lipid-binding protein, which is synthesized by the intestine and secreted into mesenteric lymph. ApoA-IV is correlated with chylomicrons and high... (Review)
Review
Apolipoprotein A-IV is lipid-binding protein, which is synthesized by the intestine and secreted into mesenteric lymph. ApoA-IV is correlated with chylomicrons and high density lipoprotein, but a large portion is free-lipoprotein, in circulation. Studies showed that apoA-IV has anti-inflammatory and anti-oxidative properties, and is able to mediate reverse cholesterol transport, which suggest that it may has anti-atherosclerotic effects and be related to protection from atherosclerotic cardiovascular disease. This article focus on current studies and the possible anti-atherogenic mechanism related to apoA-IV, in order to provide a new therapeutic target for atherosclerotic cardiovascular diseases.
Topics: Apolipoproteins A; Atherosclerosis; Cholesterol; Humans; Intestinal Mucosa; Lipid Metabolism; Lipoproteins, HDL; Protein Binding; Protein Transport
PubMed: 30352313
DOI: 10.1016/j.prostaglandins.2018.10.004 -
Atherosclerosis Apr 2020
Topics: Apolipoprotein A-I; Cardiovascular Diseases; Cholesterol, HDL; Coronary Artery Disease; Human Genetics; Humans; Mendelian Randomization Analysis
PubMed: 32178836
DOI: 10.1016/j.atherosclerosis.2020.03.005 -
Clinical Laboratory Nov 2022The purpose of this study was to investigate the association between lipoprotein(a) [Lp(a)] concentrations, apolipoprotein(a) [apo(a)] isoform, and coronary artery...
BACKGROUND
The purpose of this study was to investigate the association between lipoprotein(a) [Lp(a)] concentrations, apolipoprotein(a) [apo(a)] isoform, and coronary artery disease (CAD) stratification in Han Chinese.
METHODS
Logistic regression analysis was performed to analyze the association between Lp(a) concentrations, apo(a) isoform and CAD stratification. Lp(a) concentrations and apo(a) isoforms were combined with other risk factors to establish the optimal prediction model of CAD risk.
RESULTS
Individuals with the top quarter of Lp(a) concentrations had more than a two-fold higher risk of stable CAD and three-fold higher risk of acute coronary syndrome (ACS) compared with those in the bottom quarter. This association was no longer significant after adjustment for apo(a) isoforms in stable CAD (OR 2.198, 95% CI 0.991 - 4.875, p = 0.053), but remained significant in the ACS (OR 3.583, 95% CI 1.278 - 5.614, p < 0.05). Individuals with small apo(a) isoforms had more than a two-fold higher risk of stable CAD and almost three-fold higher risk of ACS compared with those carrying larger apo(a) isoforms; however, this association was significantly alleviated after adjustment for Lp(a) concentrations (OR 2.133, 95% CI 0.964 - 4.742, p = 0.098; OR 2.642, 95% CI 1.032 - 5.833, p = 0.298, respectively). A combination of Lp(a) concentrations and apo(a) isoforms with other risk factors was the optimal prediction model of CAD risk (AUC 0.800, 95% CI 0.752 - 0.848, p < 0.001).
CONCLUSIONS
Elevated Lp(a) concentrations and small apo(a) isoforms were significant risk factors for CAD stratification, and their effects on CAD risk were mediated by each other. Combined application of Lp(a) concentrations and apo(a) isoform with conventional risk factors could aid in the assessment and prediction of CAD.
Topics: Humans; Lipoprotein(a); Apoprotein(a); Coronary Artery Disease; Apolipoproteins A; Risk Factors; Protein Isoforms; China
PubMed: 36377991
DOI: 10.7754/Clin.Lab.2022.211232 -
Apolipoprotein A-1 as a Potential Biomarker for Solid Tumors: A Systematic Review and Meta-Analysis.Current Medicinal Chemistry 2023The diagnostic value of apolipoprotein A-I (ApoA-I) as a marker of different malignancies has been reported in several investigations; however, the results have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The diagnostic value of apolipoprotein A-I (ApoA-I) as a marker of different malignancies has been reported in several investigations; however, the results have been contradictory. The current meta-analysis examined the association between ApoA-I levels and human malignancies.
METHODS
We reviewed the databases and retrieved papers for analysis until November 1, 2021. Random-effects meta-analysis was performed to construct the pooled diagnostic parameters. To find the causes of heterogeneity, we utilized Spearman threshold effect analysis and subgroup analysis. The I2 and Chi-square tests were used to examine the heterogeneity. Moreover, subgroup analyses were performed based on sample type (serum/urine) and geographical region of study. Finally, publication bias was explored using Begg's and Egger's tests.
RESULTS
A total of 11 articles involving 4,121 participants (2,430 cases and 1,691 controls) were included. The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.764 (95% CI: 0.746 - 0.781), 0.795 (95% CI: 0.775 - 0.814), 5.105 (95% CI: 3.313 - 7.865), 0.251 (95% CI: 0.174 - 0.364), 24.61 (95% CI: 12.22 - 49.54), and 0.93, respectively. In subgroup analyses, better diagnostic values were found for urine samples and East Asian Countries (China, Korea, and Taiwan).
CONCLUSION
Urinary ApoA-I levels may serve as a favorable diagnostic marker for cancer.
Topics: Humans; Apolipoprotein A-I; Biomarkers; Neoplasms; China
PubMed: 36809959
DOI: 10.2174/0929867330666230210112700 -
MEDICC Review 2019INTRODUCTION Hypertension is one of the most studied risk factors for cardiovascular disease in adults; in children and adolescents, its global prevalence changes with...
INTRODUCTION Hypertension is one of the most studied risk factors for cardiovascular disease in adults; in children and adolescents, its global prevalence changes with age, from 1%-3% in children to 3.2% in adolescents. In adults, in addition to hypertension, several biochemical markers of cardiovascular risk have been identified. Confirming an association between these and hypertension in childhood and adolescence would allow for more timely diagnosis and monitoring of cardiovascular disease, since the presence of both the markers and hypertension would imply increased risk. OBJECTIVE Confirm an association between biochemical risk markers of cardiovascular disease and hypertension in children aged 8 to 11 years. METHODS A cross-sectional study of 373 children aged 8-11 years was conducted in 3 primary schools in the city of Santa Clara in central Cuba. The variables examined were age, sex, height, blood pressure, cholesterol, triglycerides, lipoproteins and apolipoproteins. The children were classified as normotensive, prehypertensive or hypertensive, based on blood pressure readings and percentiles for age, sex and height. Descriptive statistics were calculated for quantitative variables. A bivariate analysis, tests of independence for qualitative variables and a means comparison for quantitative variables (ANOVA and its nonparametric alternative, the Kruskal Wallis test) were performed. Fisher's F-test and its associated probability value were employed. RESULTS Some 32.2% of the children were prehypertensive and 5.1% hypertensive. Cholesterol and triglyceride values were significantly higher in hypertensive than in normotensive children (p = 0.028 and p = 0.047, respectively). HDL numbers were higher in normotensive children (p =0.001), and LDL numbers and the LDL/HDL ratio were higher in the hypertensive children, with differences between groups (p = 0.001 for both variables). There were differences between the three blood pressure categories for lipoprotein(a) and ApoA (p <0.001 and p = 0.001), for ApoB and for the ApoB/ApoA ratio (p <0.001 for both variables), with lower ApoA values and higher ApoB and ApoB/ApoA values in the hypertensive children. CONCLUSIONS The biochemical risk markers most strongly associated with hypertension in children are ApoB values, LDL, lipoprotein(a), and LDL/HDL and ApoB/ApoA ratios. KEYWORDS Adolescent, child, hypertension, apolipoproteins, cardiovascular diseases, risk factors, Cuba.
Topics: Anthropometry; Apolipoprotein B-100; Apolipoproteins A; Biomarkers; Cardiovascular Diseases; Child; Cholesterol; Cross-Sectional Studies; Cuba; Female; Humans; Hypertension; Male
PubMed: 31373579
DOI: 10.37757/MR2019.V21.N2-3.4 -
Surgery For Obesity and Related... 2015Low HDL cholesterol is an independent cardiac risk factor. A general efficacy gradient exists for the resolution of cardiovascular risk factors after bariatric surgery... (Review)
Review
Low HDL cholesterol is an independent cardiac risk factor. A general efficacy gradient exists for the resolution of cardiovascular risk factors after bariatric surgery (i.e., biliopancreatic diversion [BPD]>Roux-en-Y gastric bypass [RYGB]>sleeve gastrectomy [SG]>adjustable gastric banding [AGB]). However, a review of high level of evidence clinical studies shows a different hierarchy for the effect of bariatric surgery on HDL (i.e., RYGB=SG>BPD, AGB). Surgically induced weight loss effectively reverses many steps in HDL metabolism that have been altered with obesity. Furthermore, enterocytes contribute to HDL levels through the synthesis of apolipoproteins A-IV and A-I. RYGB and SG that preserve the small intestine (particularly the jejunum) lead to a significant rise in HDL. However, when the small intestinal contribution does not reinforce the weight loss dependent mechanisms (e.g., after BPD and AGB), only a modest rise in HDL occurs. Further experimental and clinical studies are required to better delineate the issue.
Topics: Apolipoprotein A-I; Apolipoproteins A; Bariatric Surgery; Cholesterol, HDL; Humans; Obesity; Weight Loss
PubMed: 25547050
DOI: 10.1016/j.soard.2014.07.017 -
Biochimica Et Biophysica Acta.... Feb 2017Apolipoprotein A-I (apoA-I) is a prominent member of the exchangeable apolipoprotein class of proteins, capable of transitioning between lipid-bound and lipid-free... (Review)
Review
Apolipoprotein A-I (apoA-I) is a prominent member of the exchangeable apolipoprotein class of proteins, capable of transitioning between lipid-bound and lipid-free states. It is the primary structural and functional protein of high density lipoprotein (HDL). Lipid-free apoA-I is critical to de novo HDL formation as it is the preferred substrate of the lipid transporter, ATP Binding Cassette Transporter A1 (ABCA1) Remaley et al. (2001) [1]. Lipid-free apoA-I is an important element in reverse cholesterol transport and comprehension of its structure is a core issue in our understanding of cholesterol metabolism. However, lipid-free apoA-I is highly conformationally dynamic making it a challenging subject for structural analysis. Over the past 20years there have been significant advances in overcoming the dynamic nature of lipid-free apoA-I, which have resulted in a multitude of proposed conformational models.
Topics: ATP Binding Cassette Transporter 1; Apolipoprotein A-I; Biological Transport; Cholesterol; Humans; Lipid Metabolism; Lipids
PubMed: 27890580
DOI: 10.1016/j.bbalip.2016.11.010 -
Atherosclerosis May 2022High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for cardiovascular disease. Lp(a) concentrations are an... (Review)
Review
High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for cardiovascular disease. Lp(a) concentrations are an enigmatic trait largely controlled by one single gene (LPA) that contains a complex interplay of several genetic elements with many surprising effects discussed in this review. A hypervariable coding copy number variation (the kringle IV type-2 repeat, KIV-2) generates >40 apolipoprotein(a) protein isoforms and determines the median Lp(a) concentrations. Carriers of small isoforms with up to 22 kringle IV domains have median Lp(a) concentrations up to 5 times higher than those with large isoforms (>22 kringle IV domains). The effect of the apo(a) isoforms are, however, modified by many functional single nucleotide polymorphisms (SNPs) distributed over the complete range of allele frequencies (<0.1% to >20%) with very pronounced effects on Lp(a) concentrations. A complex interaction is present between the apo(a) isoforms and LPA SNPs, with isoforms partially masking the effect of functional SNPs and, vice versa, SNPs lowering the Lp(a) concentrations of affected isoforms. This picture is further complicated by SNP-SNP interactions, a poorly understood role of other polymorphisms such as short tandem repeats and linkage structures that are poorly captured by common R values. A further layer of complexity derives from recent findings that several functional SNPs are located in the KIV-2 repeat and are thus not accessible to conventional sequencing and genotyping technologies. A critical impact of the ancestry on correlation structures and baseline Lp(a) values becomes increasingly evident. This review provides a comprehensive overview on the complex genetic architecture of the Lp(a) concentrations in plasma, a field that has made tremendous progress with the introduction of new technologies. Understanding the genetics of Lp(a) might be a key to many mysteries of Lp(a) and booster new ideas on the metabolism of Lp(a) and possible interventional targets.
Topics: Apolipoproteins A; Apoprotein(a); DNA Copy Number Variations; Kringles; Lipoprotein(a); Polymorphism, Single Nucleotide; Protein Isoforms
PubMed: 35606073
DOI: 10.1016/j.atherosclerosis.2022.04.003