High Density Lipoprotein Cholesteryl Ester Research Articles

8753 Efficacy and safety of bempedoic acid for patients with type 2 diabetes and hypercholesterolemia: a meta-analysis of randomized trials and post-hoc studies

Abstract Disclosure: A. Godoi: None. C.H. Silva: None. L.C. Hespanhol: None. P. Romeiro: None. C. Silva: None. C.A. Balieiro: None. T. Texeira: None. Background: Statins, the primary treatment for lowering LDL cholesterol and cardiovascular risk, have been associated with a worsened glycemic control. Moreover, several patients with hypercholesterolemia, including those with type 2 diabetes mellitus (T2DM), are unable to meet treatment goals with statins. Bempedoic acid (BA) has shown promising results in trials with patients with high cholesterol and cardiovascular disease, however, its efficacy in a population restricted to patients with T2DM remains unclear. Purpose: To perform a systematic review and meta-analysis comparing the therapeutic efficacy and safety of BA versus placebo in patients with T2DM and hypercholesterolemia. Methods: PubMed, Cochrane Central and Embase were systematically searched up to January 2024 include randomized controlled studies (RCTs) and post-hoc studies assessing the use of BA in a population of patients with T2DM on prior lipid-lowering therapy. Efficacy outcomes assessed were mean change in low-density lipoprotein C (LDL-C), high-density lipoprotein C (HDL-C), and non-HDL, as well as an increase in HbA1c. Safety outcomes included incidence of hyperglycemia, gout, myalgia and treatment discontinuation due to adverse events. Outcomes were pooled using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). Statistical analysis was performed with RevMan 5.4.1 and R Studio software. Heterogeneity was assessed with I² statistics. The protocol was registered in PROSPERO. Results: A total of seven RCTs with 7475 patients with T2DM were included, of whom 3842 (51.4%) were allocated to use BA and 3633 (48.6%) were allocated to placebo. Follow-up time ranged from 2 to 52 weeks. The use of BA was associated with a significantly lower LDL-C (MD -30.19mg/dL; -37.56 to -22.82 95% CI; p<0.001), and non-HDL (MD -20.05mg/dL; -20.15 to -19.95 95% CI; p<0.001), although with a lower HDL-C (MD -5.00mg/dL; -5.01 to -4.99 95% CI; p<0.001) compared to placebo. Furthermore, BA use results in significantly lower rates of myalgia (RR 0.74; 0.60 to 0.91 95%CI; p=0.004). There were no differences regarding HbA1c increase (p=0.13), treatment discontinuation (p=0.51), hyperglycemia (p-0.57), or gout (p=0.05) between groups. Conclusion: In this meta-analysis of randomized trials and post-hoc studies, the use of BA was associated with an improved lipid profile without worsening glycemic control or causing significant adverse events, although at the cost of a lower HDL-C. Presentation: 6/1/2024

Abstract P192: The Impact of Sleep Apnea on Preeclampsia or Eclampsia: The Mediation Role of Large High-Density Lipoprotein Components

Introduction: Sleep apnea is increasingly recognized as a significant risk factor for preeclampsia/eclampsia (PE). Research increasingly shows that large high-density lipoprotein (L-HDL) may influence the PE development. This study aimed to investigate the association between sleep apnea and PE and the proportion of this association that is mediated through different L-HDL components. Hypothesis: Modifications in the L-HDL components induced by sleep apnea significantly contribute to the pathogenesis of PE. Methods: A two-sample Mendelian randomization (MR) was conducted using genetic variants associated with relative sleep apnea from the FinnGen study and different L-HDL components from UK Biobank. The single-nucleotide polymorphisms (SNPs) were combined into multi-allelic models and odds ratios (ORs) and 95% confidence intervals (95% CIs) were generated using inverse-variance weighted random-effects models. Then the multivariable MR analysis was performed to estimate the effect of the mediators on the risk of PE with adjustment for sleep apnea. The MR-Egger and MR pleiotropy residual sum and outlier (MR-PRESSO) were mainly used for sensitivity analyses. In mediation analyses, the direct effect of different L-HDL components estimated in multivariable MR was compared with the total effect estimated in the main univariable MR analysis. Results: This study found that sleep apnea significantly affects the risk of PE, as well as various L-HDL components, including large high-density lipoprotein cholesterol (L-HDL-C), large high-density lipoprotein cholesteryl ester (L-HDL-CE), large high-density lipoprotein concentration (L-HDL concentration), cholesterol to total lipids ratio in large high-density lipoprotein (C/TL-L-HDL), cholesteryl esters to total lipids ratio in large high-density lipoprotein (CE/TL-L-HDL), and phospholipids to total lipids ratio in large high-density lipoprotein (P/TL-L-HDL). In multivariable MR analysis, these components were also significantly associated with the risk of PE. Additionally, mediation analysis identified P/TL-L-HDL as the only significant mediator between sleep apnea and PE (mediation effect = 0.0224; 95% CI=0.0005, 0.0443; p-value=0.0455). Conclusion: This study establishes a causal link between sleep apnea and an increased risk of preeclampsia/eclampsia, mediated by P/TL-L-HDL. Key Words: Sleep apnea; Preeclampsia; Eclampsia; Large HDL; Mendelian randomization; Mediation analysis

Diet and physical activity modification: impact on adaptive behavior and biochemical measures of children with Down syndrome

Objectives Obesity in children with Down syndrome (DS) has negative implications for behavior. The aim was to assess the influence of weight reduction by diet modification with and without physical therapy sessions on adaptive behavior and some biochemical measures in children with DS with obesity. Methods The study included 100 children with DS (56 males, 44 females; age range: 6–9 (8.5 ± 1.7) years. They were subjected to history taking, clinical examination, and the Vineland adaptive behavior scale. They were randomly divided into two groups: Group I underwent nutritional modification, and Group II was subjected to an added exercise program. The biochemical measures were estimated using the automated chemistry analyzer for blood chemistry (lipids), or ELISA. Results An elevation of behavioral adaptive scores was noticed after the weight reduction, together with a reduction in the levels of triglycerides and an elevation of high-density lipoprotein-C levels. Levels of interleukin I, interleukin 6, and leptin were reduced in both groups. However, the improvement regarding the estimated measures was greater in Group II (p < 0.05). Conclusions Weight reduction in children with DS was beneficial for their adaptive behavior and for adjusting dyslipidemia, along with some measures of inflammation. Combining physical activity with nutritional modification would help in the better advancement of the health and adaptive behavior of children with DS associated with obesity compared with isolated nutritional modification.

Urinary albumin creatinine ratio is associated with lipid profile

Moderately elevated albuminuria (30–300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have reported a relationship between moderately elevated albuminuria and triglyceride (TG) levels. Therefore, we aimed to evaluate the relationship between the urine albumin-to-creatinine ratio (UACR) and total cholesterol (TC), TG, and high-density lipoprotein C (HDL-C) levels. We analyzed data from 19,340 patients from the 2011–2014 and 2019–2020 from the Korea National Health and Nutrition Examination Surveys. Multivariate linear regression analysis showed that the UACR was positively associated with TC and TG levels and negatively associated with HDL-C levels in both Korean women and men. These results were reanalyzed according to the degree of proteinuria (normal, moderately elevated albuminuria, and severely elevated albuminuria (≥ 300 mg/g)). We found a positive relationship between UACR and TC and TG levels, but a negative association with HDL-C levels, except for TC (moderately elevated albuminuria) and HDL-C (moderately elevated albuminuria) in Korean men and TC (severely elevated albuminuria), TG (severely elevated albuminuria), and HDL-C (normal range albuminuria) in Korean women. The correlation between albuminuria and lipid profiles became more evident as albuminuria shift from normal to the severely elevated albuminuria. Thus our multivariate linear regression analysis showed that lipid profiles (TG, TC, and HDL-C levels) were associated with the UACR.

The effect of nutritional education on blood glycemic, lipidemic, and body mass index control among sample of type 2 diabetes.

Type 2 diabetes mellitus is a chronic metabolic disorder, characterized by poor glycemic control nutritional education enhances people's knowledge on healthy food choices that improve blood glycemic and lipidemic control leading to better overall health. This study is to examine the effect of nutritional education on the glycemic/lipidemic control and the body mass index in patient with type 2 diabetes mellitus. A quasi-experimental study was conducted on 40 patients with type 2 diabetes mellitus and recruited by non-probability convenience sampling method over 3months duration. BMI, HbA1c, total cholesterol, low density lipoprotein-C, high density lipoprotein-C, and triglyceride were measured at baseline and after 3months during which during which five nutritional educational lectures were done. After 3months of nutritional education, there were a significant reduction in HbA1c % from 9.53 to 8.09 (P < 0.001) and body mass index from 32.19 to 31.58 (P = 0.001) and also slight but non-significant changes in cholesterol, LDL, triglyceride, and HDL (7.05 ± 38.428, 5.00 ± 29.858, 9.10 ± 85.386, 0.24 ± 3.612 respectively) (P = 0.253, 0.296, 0.668, and 0.504 respectively). Nutritional education program is effective to decrease HbA1c % and body mass index.

Total Outflow of High-Density Lipoprotein–Cholesteryl Esters from Plasma Is Decreased in a Model of 3/4 Renal Mass Reduction

(1) Background: Previous studies have enriched high-density lipoproteins (HDL) using cholesteryl esters in rabbits with a three-quarter reduction in functional renal mass, suggesting that the kidneys participate in the cholesterol homeostasis of these lipoproteins. However, the possible role of the kidneys in lipoprotein metabolism is still controversial. To understand the role of the kidneys in regulating the HDL lipid content, we determined the turnover of HDL-cholesteryl esters in rabbits with a three-quarter renal mass reduction. (2) Methods: HDL subclass characterization was conducted, and the kinetics of plasma HDL-cholesteryl esters, labeled with tritium, were studied in rabbits with a 75% reduction in functional renal mass (Ntx). (3) Results: The reduced renal mass triggered the enrichment of cholesterol, specifically cholesteryl esters, in HDL subclasses. The exchange of cholesteryl esters between HDL and apo B-containing lipoproteins (VLDL/LDL) was not significantly modified in Ntx rabbits. Moreover, the cholesteryl esters of HDL and VLDL/LDL fluxes from the plasmatic compartment tended to decrease, but they only reached statistical significance when both fluxes were added to the Nxt group. Accordingly, the fractional catabolic rate (FCR) of the HDL-cholesteryl esters was lower in Ntx rabbits, concomitantly with its accumulation in HDL subclasses, probably because of the reduced mass of renal cells requiring this lipid from lipoproteins.

CRISPR/Cas9-mediated knockout of the Vanin-1 gene in the Leghorn Male Hepatoma cell line and its effects on lipid metabolism.

Vanin-1 (VNN1) is a pantetheinase that catalyses the hydrolysis of pantetheine to produce pantothenic acid and cysteamine. Our previous studies have shown that the VNN1 is specifically expressed in chicken liver which negatively regulated by microRNA-122. However, the functions of the VNN1 in lipid metabolism in chicken liver haven't been elucidated. First, we detected the VNN1 mRNA expression in 4-week chickens which were fasted 24 hours. Next, knocked out VNN1 via CRISPR/Cas9 system in the chicken Leghorn Male Hepatoma cell line. Detected the lipid deposition via oil red staining and analysis the content of triglycerides (TG), low-density lipoprotein-C (LDL-C), and highdensity lipoprotein-C (HDL-C) after VNN1 knockout in Leghorn Male Hepatoma cell line. Then we captured various differentially expressed genes (DEGs) between VNN1-modified LMH cells and original LMH cells by RNA-seq. Firstly, fasting-induced expression of VNN1. Meanwhile, we successfully used the CRISPR/Cas9 system to achieve targeted mutations of the VNN1 in the chicken LMH cell line. Moreover, the expression level of VNN1 mRNA in LMH-KO-VNN1 cells decreased compared with that in the wild-type LMH cells (p<0.0001). Compared with control, lipid deposition was decreased after knockout VNN1 via oil red staining, meanwhile, the contents of TG and LDL-C were significantly reduced, and the content of HDL-C was increased in LMH-KO-VNN1 cells. Transcriptome sequencing showed that there were 1,335 DEGs between LMH-KO-VNN1 cells and original LMH cells. Of these DEGs, 431 were upregulated, and 904 were downregulated. Gene ontology analyses of all DEGs showed that the lipid metabolism-related pathways, such as fatty acid biosynthesis and long-chain fatty acid biosynthesis, were enriched. KEGG pathway analyses showed that "lipid metabolism pathway", "energy metabolism", and "carbohydrate metabolism" were enriched. A total of 76 DEGs were involved in these pathways, of which 29 genes were upregulated (such as cytochrome P450 family 7 subfamily A member 1, ELOVL fatty acid elongase 2, and apolipoprotein A4) and 47 genes were downregulated (such as phosphoenolpyruvate carboxykinase 1) by VNN1 knockout in the LMH cells. These results suggest that VNN1 plays an important role in coordinating lipid metabolism in the chicken liver.

Common risk factors for dental caries and impaired glucose regulation in Guangxi, China.

To assess the prevalence of caries and impaired glucose regulation (IGR) and try to investigate their common risk factors among adult residents in Guangxi province. A cross-sectional study was conducted on a sample of 2993 adults from five different areas of Guangxi province. The sociodemographic data, history of personal habits such as diet and physical activities, physical measurements, oral examination results and biochemical laboratory test data were collected to establish a database and prepare a sound research model. Chi-square test and multiple logistic regression were used to analyse the risk factors for dental caries and IGR. The prevalence rate for caries was 85.9%, and the mean DMFT score was 7.35. In multiple logistic regression, after adjustment, education level, occupation, daily consumption of vegetables, weekly consumption of carbonated beverages and weekly exercise were associated with caries (odds ratio [OR]: 2.10, OR: 1.80, OR: 1.40, OR: 2.45, OR: 2.38). The prevalence of IGR was 33.5%, and after adjustment, results showed that occupation, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, high-density lipoprotein-C levels and low-density lipoprotein-C levels were significantly associated with IGR (OR: 0.80, OR: 1.70, OR: 1.56, OR: 1.88, OR: 1.60, OR: 1.43, OR: 1.48). The strength of association between caries/IGR and risk factors was a weak association or moderate association. We have not found common risk factors between dental caries and IGR. Therefore, further studies are needed to explore these common risk factors to prevent caries and IGR.

Elevated circulating follicle stimulating hormone level is associated with dyslipidemia in male type 2 diabetes mellitus patients: A cross-sectional study.

Type 2 diabetes mellitus (T2DM) commonly combines with dyslipidemia, and both are known as the risk factors of cardiovascular events and aggravate the arteriosclerosis progression. In this study, we investigated the relationship between follicle-stimulating hormone (FSH) and lipid profiles in male T2DM patients. We collected clinical data of male T2DM patients in the Chinese Han population hospitalised from January 2018 to June 2020. A total of 963 patients with a mean age of 58.89±12.25years old were enroled in this study. The results showed that the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL)-C levels were decreased gradually from the highest quartile groups (Q4) to Q1 group relevant to luteinising hormone and FSH, and no significant difference was observed in high-density lipoprotein-C levels among Q4-Q1 groups. Sub-groups analysis showed that, with the increased FSH level, TC, TG, and LDL-C levels were increased in the elder group (40-59years old) than those in the younger group (20-39years old). Spearman's analysis revealed a positive correlation between FSH and the levels of TC, TG, and LDL-C (r=0.354, r=0.336, r=0.312, p<0.001, respectively). The effect of FSH is independent of the changes in total testosterone level. Multivariate analysis found that increased FSH levels (≥9.26mIU/mL) and decreased total testosterone levels (<13.30nmol/L) were positively correlated with high TC, TG, and LDL-Cemia (OR=4.014, 1.565, 1.602, 1.660, 2.127, 1.322, respectively, p<0.05). Our data suggest that high serum FSH level in male T2DM patients could be a potential independent risk factor correlated with the elevated TC, TG, and LDL-C.

Vitamin D Deficiency and Its Association With Cardiovascular Diseases Among Patients Attending a Private Tertiary Sector Cardiovascular Heart Clinic in Nairobi.

Vitamin D deficiency is a common condition that affects approximately 30-50% of the worldwide population. Vitamin D deficiency is associated with an increased risk of cardiometabolic diseases and is considered a cardiovascular risk factor globally. Methods: This is a retrospective cross-sectional study that aimed to identify the prevalence of vitamin D deficiency and its associations with the cardiovascular disease (CVD) risk profile of patients presenting for cardiac evaluation at Primecare Heart Clinic, a private heart clinic in Nairobi, Kenya, between January 1, 2020 and January 31, 2022. Females with vitamin D deficiency composed 58.87% of the study participants. The average 10-year Framingham CVD risk level of the vitamin D-deficient participants was 7.09%. Participants with vitamin D deficiency that were older and had low serum high-density lipoprotein C (HDL-C) levels and high systolic blood pressure (BP) had a higher risk of CVDs. Male participants were at five times higher risk of CVDs.Vitamin D-deficient patients who were older and had a low HDL cholesterol level and high systolic BP are at a high risk of CVDs. The two-way analysis of variance (ANOVA) test value was 345.6992, and the p-valuewas 0.002884. Our study demonstrated that a low level of vitamin D was associated with a higher Framingham cardiovascular risk score and cardiovascular risk in patients. Nonetheless, this is a retrospective study, which is a major limitation of this study.

Lipids and Transaminase in Antiretroviral-Treatment-Experienced People Living with HIV, Switching to a Doravirine-Based vs. a Rilpivirine-Based Regimen: Data from a Real-Life Setting

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load &lt; 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (−0.36, p &lt; 0.0001) than in the RPV cohort (−0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT &gt; 40 IU/L experienced a significant decline (−14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART.

Sex/gender differences in metabolic syndrome among cancer survivors in the US: an NHANES analysis

BackgroundThe purpose of this study was to assess the association of metabolic syndrome (MetS) and its individual components in cancer survivors (CS) by gender, in comparison to participants without a history of cancer who have at least one chronic disease (CD) and those without a chronic disease diagnosis (NCD).MethodsData from participants 40 years and older (n = 12,734) were collected from the 2011 to 2018 National Health and Nutrition Examination Survey dataset. MetS was defined based on the National Cholesterol Education Program’s Adult Treatment Panel III. Chi-square test and multivariate-adjusted logistic regression was used to assess group comparisons and associations respectively.ResultsCompared to NCD, CS and CD men had increased odds of meeting MetS, OR 2.60 (CI 1.75–3.87) and OR 2.18 (CI 1.59–2.98) respectively. For women, CS and CD participants also had higher odds of meeting MetS criteria compared to their healthy counterparts, OR 2.05 (CI 1.44–2.93) and OR 2.14 (CI 1.63–2.81) respectively. In subgroup analysis by cancer site, CS men with a history of hematologic malignancies (OR 4.88, CI 1.30–18.37) and CS women with cervical cancer (OR 4.25, CI 1.70–10.59) had highest odds of developing MetS, compared to NCD. CS men also showed a strong association with elevated waist circumference, low high density lipoprotein-c, and elevated triglycerides, even by cancer site, but there were no consistent findings among women.ConclusionThis study indicates that CS men have a strong association with MetS, especially among those with blood-related cancers.

Measurement of Serum Low Density Lipoprotein Cholesterol and Triglyceride-Rich Remnant Cholesterol as Independent Predictors of Atherosclerotic Cardiovascular Disease: Possibilities and Limitations

The serum low density lipoprotein cholesterol (LDL-C) concentration is the dominant clinical parameter to judge a patient’s risk of developing cardiovascular disease (CVD). Recent evidence supports the theory that cholesterol in serum triglyceride-rich lipoproteins (TRLs) contributes significantly to the atherogenic risk, independent of LDL-C. Therefore, combined analysis of both targets and adequate treatment may improve prevention of CVD. The validity of TRL-C calculation is solely dependent on the accuracy of the LDL-C measurement. Direct measurement of serum LDL- C is more accurate than established estimation procedures based upon Friedewald, Martin–Hopkins, or Sampson equations. TRL-C can be easily calculated as total C minus high density lipoprotein C (HDL-C) minus LDL-C. Enhanced serum LDL-C or TRL-C concentrations require different therapeutic approaches to lower the atherogenic lipoprotein C. This review describes the different atherogenic lipoproteins and their possible analytical properties and limitations.

Predictive value of triglycerides to high density lipoprotein ratio in patients with first attack of acute coronary syndrome.

To identify patients who are at risk for a first cardiovascular event, mitigate the risk, and institute early intervention. The triglyceride to high-density lipoprotein-C (TG/HDL-C) ratio has been found to be a very useful biomarker for directing treatment and prevention therapy. This retrospective cross-sectional study included adult patients (aged >18 years) experiencing first-time acute coronary syndrome (ACS). We examined all patient databases for a definite diagnosis of angina, non-ST segment elevation myocardial infarction (NSTEMI), or ST-segment elevation myocardial infarction (STEMI). Lipid profiles were obtained prior to or at the time of admission. A total of 265 patients were included in the study (mean age 57.83 ± 11.4 years) and 79.2% were men. Male gender, presence of diabetes, raised total cholesterol, raised low-density lipoprotein (LDL), and raised troponin level on admission were significantly positively correlated with STEMI (p=0.004, p=0.001, p<0.001, and p<0.001), whereas TG/HDL-C ratio was significantly negatively correlated with STEMI (p=0.048), while there was no significant results with NSTEMI (p=0.264) and angina (p=0.326). Total cholesterol and raised low-density lipoprotein (LDL) were significantly positively correlated with NSTEMI (p=0.013 and p=0.024). Patients with first-time ACS may not have an increased TG/HDL-C ratio. High LDL levels had the most significant association with an ACS event, along with total cholesterol and diabetes. Further research is needed on a larger scale to determine the association of TG/HDL-C ratio with ACS and differentiate the different types of ACS events according to their clinical and laboratory characteristics.

Evaluation of the relationship between monocyte to high-density lipoprotein cholesterol ratio and thrombus burden in patients with deep vein thrombosis

The purpose of this study was to evaluate monocyte count and high-density lipoprotein cholesterol levels and their ratio (monocyte/high-density lipoprotein ratio) in patients with deep venous thrombosis as well as to determine whether this ratio at the time of diagnosis can be an indicator of thrombus burden in terms of thrombus location in deep venous thrombosis. We retrospectively analyzed the patient's diagnosis of deep venous thrombosis confirmed with venous Doppler ultrasound, using a database query for outpatients between 2018 and 2022. Of 378 patients included, blood count results at the time of diagnosis were available for 356. We recruited 300 age- and sex-matched patients with appropriate blood counts, without a diagnosis of deep venous thrombosis, as the control group, by querying the outpatient clinic database. The monocyte/high-density lipoprotein ratio was computed from the ratio of monocyte count to high-density lipoprotein-C. Patients were categorized based on the level of thrombus and the number of vein segments involved as evidenced by Doppler ultrasound findings. The serum level of monocyte/high-density lipoprotein ratio was significantly higher in the patient group compared to the control group (p<0.01). Patients with proximal deep venous thrombosis had a higher mean monocyte/high-density lipoprotein ratio (19.6±5.1 vs. 17.1±5.5; p<0.01) than patients with distal deep venous thrombosis. Monocyte/high-density lipoprotein ratio increased with the number of vein segments involved (p<0.01). Monocyte/high-density lipoprotein ratio is significantly elevated in patients with deep venous thrombosis when compared to the control group. Monocyte/high-density lipoprotein ratio levels were correlated with disease burden reflected by thrombus location and the number of vein segments involved in deep venous thrombosis patients.

The Role of Exercise on Cardiometabolic Profile and Body Composition in Youth with Type 1 Diabetes.

Exercise has a direct positive effect on glycemic control by promoting insulin secretion from β-pancreatic islet-cells and by increasing skeletal muscle glucose uptake. The reduction in daily insulin needs and the optimization of glycemic control improves the patient's quality of life, self-esteem, mental wellness, as well as diabetes-related mobility and mortality. The aim of this study was to investigate the effect of physical activity in children and adolescents with type-1 diabetes (T1D) on diabetic control, cardiovascular, and biochemical profiles; hs-CRP; IL6; leptin; and adiponectin levels of the population under study. This is a prospective cross-sectional study that involved 80 participants (36 boys and 44 girls) with T1D, who were aged 6-21 years and who attended the Diabetes and Metabolism Clinic of the 2nd Pediatric Department, University of Athens, "P & A Kyriakou" Children's Hospital of Athens. Twenty (25%) children were above the 75th percentile regarding total levels of physical activity, while 40 (50%) and 20 (25%) were between the 25th and 75th percentile, as well as below the 25th percentile, respectively. In the group with an intermediate level of exercise, physical activity was negatively associated with the participant's family situation (traditional, single parent, grandparent, with others, or by himself/herself) (p = 0.013), ferritin (p = 0.031), lipoprotein(a) [Lp(a)] (p = 0.016), and squared leptin levels (p = 0.040). Whereas in the groups with extreme vs. no exercise there was a negative association with the number of daily glucose measurements (p = 0.047). However, in the group with non-vigorous exercise, physical activity was positively associated with high density lipoprotein-c (HDL-c) levels (p = 0.048). The findings of this study are indicative of the beneficial role of exercise on children and adolescents with T1D, which is achieved by primarily improving their cardiometabolic profile through the amelioration of lipid profile [HDL-c, Lp(a)] and leptin levels, as well as by reducing chronic systemic inflammatory response (ferritin) and ultimately decreasing the overall diabetes morbidity.

The Distinct Role of the HDL Receptor SR-BI in Cholesterol Homeostasis of Human Placental Arterial and Venous Endothelial Cells.

As opposed to adults, high-density lipoprotein (HDL) is the main cholesterol carrying lipoprotein in fetal circulation. The major HDL receptor, scavenger receptor class B type I (SR-BI), contributes to local cholesterol homeostasis. Arterial endothelial cells (ECA) from human placenta are enriched with cholesterol compared to venous endothelial cells (ECV). Moreover, umbilical venous and arterial plasma cholesterol levels differ markedly. We tested the hypothesis that the uptake of HDL-cholesteryl esters differs between ECA and ECV because of the differential expression of SR-BI. We aimed to identify the key regulators underlying these differences and the functional consequences. Immunohistochemistry was used for visualization of SR-BI in situ. ECA and ECV were isolated from the chorionic plate of human placenta and used for RT-qPCR, Western Blot, and HDL uptake assays with 3H- and 125I-labeled HDL. DNA was extracted for the methylation profiling of the SR-BI promoter. SR-BI regulation was studied by exposing ECA and ECV to differential oxygen concentrations or shear stress. Our results show elevated SR-BI expression and protein abundance in ECA compared to ECV in situ and in vitro. Immunohistochemistry demonstrated that SR-BI is mainly expressed on the apical side of placental endothelial cells in situ, allowing interaction with mature HDL circulating in the fetal blood. This was functionally linked to a higher increase of selective cholesterol ester uptake from fetal HDL in ECA than in ECV, and resulted in increased cholesterol availability in ECA. SR-BI expression on ECV tended to decrease with shear stress, which, together with heterogeneous immunostaining, suggests that SR-BI expression is locally regulated in the placental vasculature. In addition, hypomethylation of several CpG sites within the SR-BI promoter region might contribute to differential expression of SR-BI between chorionic arteries and veins. Therefore, SR-BI contributes to a local cholesterol homeostasis in ECA and ECV of the human feto-placental vasculature.

Bile Acid Sequestrants for Hypercholesterolemia Treatment Using Sustainable Biopolymers: Recent Advances and Future Perspectives.

Bile acids, the endogenous steroid nucleus containing signaling molecules, are responsible for the regulation of multiple metabolic processes, including lipoprotein and glucose metabolism to maintain homeostasis. Within our body, they are directly produced from their immediate precursors, cholesterol C (low-density lipoprotein C, LDL-C), through the enzymatic catabolic process mediated by 7-α-hydroxylase (CYP7A1). Bile acid sequestrants (BASs) or amphiphilic resins that are nonabsorbable to the human body (being complex high molecular weight polymers/electrolytes) are one of the classes of drugs used to treat hypercholesterolemia (a high plasma cholesterol level) or dyslipidemia (lipid abnormalities in the body); thus, they have been used clinically for more than 50 years with strong safety profiles as demonstrated by the Lipid Research Council-Cardiovascular Primary Prevention Trial (LRC-CPPT). They reduce plasma LDL-C and can slightly increase high-density lipoprotein C (HDL-C) levels, whereas many of the recent clinical studies have demonstrated that they can reduce glucose levels in patients with type 2 diabetes mellitus (T2DM). However, due to higher daily dosage requirements, lower efficacy in LDL-C reduction, and concomitant drug malabsorption, research to develop an "ideal" BAS from sustainable or natural sources with better LDL-C lowering efficacy and glucose regulations and lower side effects is being pursued. This Review discusses some recent developments and their corresponding efficacies as bile removal or LDL-C reduction of natural biopolymer (polysaccharide)-based compounds.

HDL maturation and remodelling

Cholesterol in the circulation is mostly transported in an esterified form as a component of lipoproteins. The majority of these cholesteryl esters are produced in nascent, discoidal high density lipoproteins (HDLs) by the enzyme, lecithin:cholesterol acyltransferase (LCAT). Discoidal HDLs are discrete populations of particles that consist of a phospholipid bilayer, the hydrophobic acyl chains of which are shielded from the aqueous environment by apolipoproteins that also confer water solubility on the particles. The progressive LCAT-mediated accumulation of cholesteryl esters in discoidal HDLs generates the spherical HDLs that predominate in normal human plasma. Spherical HDLs contain a core of water insoluble, neutral lipids (cholesteryl esters and triglycerides) that is surrounded by a surface monolayer of phospholipids with which apolipoproteins associate. Although spherical HDLs all have the same basic structure, they are extremely diverse in size, composition, and function. This review is concerned with how the biogenesis of discoidal and spherical HDLs is regulated and the mechanistic basis of their size and compositional heterogeneity. Current understanding of the impact of this heterogeneity on the therapeutic potential of HDLs of varying size and composition is also addressed in the context of several disease states.

HDL and Cholesterol Ester Transfer Protein (CETP).

Cholesterol ester transfer protein (CETP) is important clinically and is one of the major targets in cardiovascular disease studies. With high conformational flexibility, its tunnel structure allows unforced movement of high-density lipoproteins (HDLs), VLDLs, and LDLs. Research in reverse cholesterol transports (RCT) reveals that the regulation of CETP activity can change the concentration of cholesteryl esters (CE) in HDLs, VLDLs, and LDLs. These molecular insights demonstrate the mechanisms of CETP activities and manifest the correlation between CETP and HDL. However, animal and cell experiments focused on CETP give controversial results. Inhibiting CETP is found to be beneficial to anti-atherosclerosis in terms of increasing plasma HDL-C, while it is also claimed that CETP weakens atherosclerosis formation by promoting RCT. Currently, the CETP-related drugs are still immature. Research on CETP inhibitors is targeted at improving efficacy and minimizing adverse reactions. As for CETP agonists, research has proved that they also can be used to resist atherosclerosis.