Effects Of High-density Lipoprotein Research Articles

Blood Lead and High-Density Lipoprotein Concentrations in Relation to Human Blood Pressure: A Cross Sectional Study.

BackgroundWhile the relationship between blood pressure and blood lead has been studied more extensively, the effect of high-density lipoprotein (HDL) concentration on this relationship remains uncertain. Therefore, this study aimed to determine the effect of HDL concentration on the relationship between blood lead and blood pressure.MethodsThe research used cross-sectional data from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES), which included 16,451 participants aged 20–60 years. Multivariable linear regression was used to evaluate the correlation among blood lead, systolic blood pressure (SBP), and diastolic blood pressure (DBP). HDL concentration was determined by low HDL concentration (≤ 49 mg/dl) and high HDL concentration (>49 mg/dl) stratified. The effect of HDL concentration was assessed by an interaction test between blood lead and SBP in multivariable linear regression.ResultsIn this cross-sectional research, we identified a positive correlation between blood lead and SBP, but not DBP. The relationship between blood lead and SBP was different in the group with low and high HDL concentrations (β: 0.21 95% Cl:−0.05-0.46 vs. β:0.47 95% Cl: 0.15-0.79). In addition, high HDL significantly altered the positive correlation between blood lead and SBP (P-value of interaction < 0.001).ConclusionThe study suggests an interaction between HDL and blood lead in elevating SBP, which may have important clinical implications.

Measures of high-density lipoprotein function in men and women with severe aortic stenosis

BackgroundCalcification of the aortic valve is a common heart valve disorder, in some cases leading to clinically impactful severe aortic stenosis (AS). Sex-specific differences in aortic valve calcification (ACV) exist, with women having a lower burden of calcification than men as measured by computed tomography; however, the pathophysiological mechanism that leads to these differences remains unclear.MethodsUsing cultured human Tamm-Horsfall protein 1 (THP-1) macrophages and human aortic valve interstitial cells, the effects of high-density lipoprotein (HDL) particles isolated from the plasma of men and women with severe AS were studied for cholesterol efflux capacity (CEC).ResultsHDL-CEC was assessed in 46 patients with severe AS, n = 30 men, n = 16 women. ATP-Binding Cassette A1 (ABCA1)-mediated HDL-CEC was measured from human cultured THP-1 macrophages to plasma HDL samples. Women with severe AS had more ABCA1-mediated HDL-CEC, as compared to men (8.50 ± 3.90% cpm vs. 6.80 ± 1.50% cpm, P = 0.04). HDL pre-β1 and α-particles were higher in woman than in men by spectral density, (pre-β1 HDL, 20298.29 ± 1076.15 vs. 15,661.74 ± 789.00, P = 0.002, and α-HDL, 63006.35 ± 756.81 vs. 50,447.00 ± 546.52, P = 0.03). Lecithin-cholesterol acyltransferase conversion of free cholesterol into cholesteryl esters was higher in women than men (16.44 ± 9.11%/h vs. 12.00 ± 8.07%/h, P = 0.03).ConclusionsSex-specific changes in various parameters of HDL-CEC were found in patients with severe AS. Sex-based modifications in HDL functionality by HDL-CEC might account for the reduced burden of calcification in women vs. men with severe AS. Therefore, future studies should target sex-related pathways in AS to help to improve understanding and treatment of AS.Graphical abstractSex specifc differences in AVC and differences associated with HDL function in men and women with severe AS. When compared to men, women had higher preβ-HDL and α-HDL migrating particles, higher cholesterol efflux to HDL, and higher lecithin cholesterol acyl transferase (LCAT) activity, possibly indicating that improved reverse cholesterol transport may be protective against worsened calcification.

Mathematical modeling of atherogenesis: Atheroprotective role of HDL

Atherosclerosis is a chronic inflammatory cardiovascular disease in which arteries harden through the build-up of plaques. This work is devoted to the mathematical modeling and analysis of the inflammatory process of atherosclerosis. We propose a mathematical model formed by three coupled partial differential equations of reaction-diffusion type. We take into account three key-role players: the inflammatory immune cells, the inflammatory cytokines and the oxidized low density lipoproteins. A stability analysis of the kinetic system is performed. It leads to the presence of three stable fixed points relevant to appropriate biological states of atherogenesis; no inflammation, stabilized inflammation (stable plaque) and advanced inflammation (vulnerable plaque). The cases that may occur are subject to the variation of the parameters values. A detailed discussion showing how the model fits the biological phenomena is then established. We investigate as well the existence of solutions of traveling waves type along with numerical simulations that show the wave propagation in different cases. This shows that the inflammatory process propagates inside the intima as a traveling wave. Then, we consider the effect of high density lipoprotein (HDL) on the atherosclerotic plaque formation. To do that, we elaborate a map that determines the level of risk of plaque formation with respect to the prevalence of HDL in the blood. These results confirm but also generalize previous results published in the literature. They also give a deeper understanding to the propagation of the inflammation inside the artery in terms of the interplay among the different main players in the whole process.

Effect of high-density lipoprotein on penile erection: A cross-sectional study.

Previous studies have shown that elevated levels of high-density lipoprotein (HDL) could inhibit penile erection, but the relationship between HDL and the erection of the penile tip or base has not been extensively researched. We investigated the effects of HDL on erection of the penile tip and base through a cross-sectional study of 113 patients with erectile dysfunction, using a cut-off score of ≤21 on the International Index of Erectile Function-5. The following patient data were collected: nocturnal penile tumescence; blood pressure; platelet count; platelet distribution width; mean platelet volume; plateletcrit; and levels of serum glucose, total cholesterol, triglyceride, HDL, and low-density lipoprotein. Univariate and multivariate analyses were used to assess the association between HDL levels and the erection of the penile tip and base. We confirmed that HDL had a beneficial effect on penile erectile function. We also found that when the HDL level exceeded the normal range, the change in HDL had a significant effect on the penile base. In addition, our study did not find any relationship between platelet parameters and erection of the penile tip or penile base.

Effect of High-Density Lipoprotein from Healthy Subjects and Chronic Kidney Disease Patients on the CD14 Expression on Polymorphonuclear Leukocytes.

In uremic patients, high-density lipoprotein (HDL) loses its anti-inflammatory features and can even become pro-inflammatory due to an altered protein composition. In chronic kidney disease (CKD), impaired functions of polymorphonuclear leukocytes (PMNLs) contribute to inflammation and an increased risk of cardiovascular disease. This study investigated the effect of HDL from CKD and hemodialysis (HD) patients on the CD14 expression on PMNLs. HDL was isolated using a one-step density gradient centrifugation. Isolation of PMNLs was carried out by discontinuous Ficoll-Hypaque density gradient centrifugation. CD14 surface expression was quantified by flow cytometry. The activity of the small GTPase Rac1 was determined by means of an activation pull-down assay. HDL increased the CD14 surface expression on PMNLs. This effect was more pronounced for HDL isolated from uremic patients. The acute phase protein serum amyloid A (SAA) caused higher CD14 expression, while SAA as part of an HDL particle did not. Lipid raft disruption with methyl-β-cyclodextrin led to a reduced CD14 expression in the absence and presence of HDL. HDL from healthy subjects but not from HD patients decreased the activity of Rac1. Considering the known anti-inflammatory effects of HDL, the finding that even HDL from healthy subjects increased the CD14 expression was unexpected. The pathophysiological relevance of this result needs further investigation.

The effects of high-density lipoprotein and oxidized high-density lipoprotein on forskolin-induced syncytialization of BeWo cells

IntroductionThe negative relationship between maternal high-density lipoprotein-cholesterol (HDL-c) level during pregnancy and infant birth weight has been found. Syncytialization (differentiation and fusion) of trophoblast cells is important to fetal development. HDL has an antioxidant effect, and has been proved to protect trophoblast functions including hormone secretion and invasion. However, HDL is susceptible to oxidation, and high concentrations of HDL impair cell growth and oxidized HDL (oxHDL) inhibits cell proliferation and migration. Moreover, the effects of HDL and oxHDL on trophoblast syncytialization have not been characterized. The aim of this study was to investigate the effects of HDL and oxHDL on trophoblast syncytialization. MethodsHuman choriocarcinoma trophoblasts (BeWo cells) were treated with human HDL or oxHDL and then induced to differentiate by forskolin in syncytialization assays. Expression levels of mRNAs and proteins regulating syncytialization were detected by real-time PCR and western blotting, respectively. ResultsTreatments of HDL at high concentrations reduced human chorionic gonadotropin (hCG) secretion, placental alkaline phosphatase activity and fusion rates, and decreased the expressions of GCM1 and ERVW-1 mRNA as well as phospho-MAPK1/3 (p-MAPK1/3) and total MAPK1/3 protein in the forskolin-induced syncytialization of BeWo cells. Furthermore, treatment of oxHDL (20 μg/ml) decreased hCG secretion, but increased the expression of p-MAPK1/3 protein. DiscussionThese data suggested that both HDL at high concentrations and oxHDL inhibited BeWo cells syncytialization, and might be harmful to placental and fetal development.

Lipid Profile Alterations during Fingolimod Treatment in Multiple Sclerosis Patients

Fingolimod reduces inflammatory activity in multiple sclerosis (MS) by acting as a functional antagonist of sphingosine 1-phosphate (S1P) receptors. It has been suggested that S1P might also contribute to the antiatherogenic effect of high-density lipoprotein (HDL). We conducted a retrospective observational study using data of 72 MS patients from two Finnish hospital districts to find out whether lipid profiles change during treatment with fingolimod. A mixed-effects model with patient as a random effect was used to analyze lipid profile alterations. We found a statistically significant elevation in both total cholesterol (0.12 mmol/L per year) and HDL (0.04 mmol/L per year) during a median follow-up of 12 months, while low-density lipoprotein (LDL) and triglycerides remained unchanged. Since the mean elevation observed in both lipid values seems to be modest, we suggest that routine lipid profile monitoring is unnecessary during fingolimod treatment in MS patients without pre-existing cardiovascular comorbidities. Graphical abstract.

Effect of High Density Lipoprotein and Body Mass Index on Gastric Cancer by Gender, Site, and Stage: A Nationwide Study

Effect of High Density Lipoprotein and Body Mass Index on Gastric Cancer by Gender, Site, and Stage: A Nationwide Study

Predictive effect of high density lipoprotein on acute kidney injury after adult heart surgery

Objective To investigate the effect of preoperative serum high-density lipoprotein on acute kidney injury (AKI) after cardiac surgery. Methods A retrospective analysis of 295 cases of adult patients undergoing cardiopulmonary bypass during our hospital from March 2017 to May 2017 was retrospectively analyzed. According to whether AKI was divided into two groups, AKI group(n=40) and non-AKI group(n=255). The clinical data were collected and the risk factors of AKI were analyzed by single factor and multivariate logistic regression. Results Five patients(12.5%) in the AKI group underwent bedside continuous renal replacement therapy (CRRT), 5 died in the AKI group, and 5 patients died in the non-AKI group. Multivariate logistic regression analysis showed that the high-density lipoprotein content was lower than the normal value of 1 mmol/L in patients with age, sex(male), comorbidities (hypertension and diabetes mellitus), cardiopulmonary bypass and preoperative uric acid value>420 μmol/L was also an independent risk factor for AKI after cardiopulmonary bypass. Conclusions AKI is a common complication after cardiopulmonary bypass in adults. Preoperative serum high-density lipoprotein less than 1 mmol / L can increase the probability of occurrence of AKI after surgery. Key words: Acute Kidney Injury; Cardiac Surgical Procedures; Lipoproteins, HDL

To study the effect of high density lipoprotein and calcium on the levels of random blood sugar, body mass index, and age: A case control perspective

To study the effect of high density lipoprotein and calcium on the levels of random blood sugar, body mass index, and age: A case control perspective

Effect of Helicobacter pylori eradication and high-density lipoprotein on the risk of de novo gastric cancer development

The effect of Helicobacter pylori eradication on de novo gastric cancer is controversial, although meta-analyses suggest a reduction in gastric cancer after eradication. The effect of high-density lipoprotein (HDL) on gastric cancer has been rarely reported. In this large retrospective cohort study, participants underwent endoscopy and H pylori testing from 2003 to 2011 and underwent follow-up endoscopy and H pylori testing until 2013. H pylori infection was detected using a rapid urease test or histologic test. The H pylori eradication group was defined as successful eradication, whereas the H pylori persistent group was defined as noneradication or eradication failure. The risk of cancer was measured with hazard ratios (HRs) and 95% confidence intervals (CIs). Among 10,328 healthy subjects (5951 men; mean age, 48.7 years), 31 gastric cancers were detected during a median follow-up of 5.5 years. De novo gastric cancer developed in 21 of 3508 subjects (.6%) in the noneradication group, 4 of 2050 subjects (.2%) in the successful eradication group, and 6 of 4770 participants (.13%) in the absence of H pylori group. In the adjusted analysis, H pylori eradication decreased de novo gastric cancer risk (HR, .29; 95% CI, .10-.86) compared with the persistent group. The risk of de novo gastric cancer in absence of H pylori was also much lower compared with the persistent group (HR, .24; 95% CI, .09-.60). Low serum HDL increased the risk of de novo gastric cancer (HR, 2.67; 95% CI, 1.14-6.16). Successful H pylori eradication reduced de novo gastric cancer, whereas low HDL increased its risk.

High Density Lipoprotein from Egg Yolk (EYHDL) Improves Dyslipidemia by Mediating Fatty Acids Metabolism in High Fat Diet-induced Obese Mice.

We investigated the effect of high density lipoprotein from egg yolk (EYHDL) on serum, hepatic and fecal lipid and fatty acids (FAs) levels and on gene expression involved in FAs metabolism. Male KM mice were fed either normal diet (ND; n=20), high fat diet (HFD; n=20), or high fat diet containing EYHDL (EYHDL; 0.6 mg/g, every day by oral gavage, n=20) for 100 days. At the end of the experiment, the effects of treatments on biochemical parameters, FAs profiles and involved gene expression were analyzed. Our results revealed that EYHDL markedly suppressed the body weight gain, accumulation of abdominal fat tissues, serum concentrations of LDL-cholesterol (LDL-C) and triglycerides, hepatic triglycerides and cholesterol accumulation, while increased serum concentration of HDL-cholesterol (HDL-C). EYHDL intake also increased total cholesterol (TC) excretions compared with HFD group. Moreover, it alleviated the severity of fatty liver and improved glucose and insulin tolerance compared with HFD. More importantly, EYHDL partially normalized FAs profiles in serum, liver and fecaces and neutralized the HFD-induced upregulation of SREBP-1c, Acaca, Fasn, GPAT and Scd1. In conclusion, our findings indicate that EYHDL may have the potential to improve metabolic disturbances that occur in HFD mice and can be considered as an appropriate dietary recommendation for the treatment of metabolic syndrome (MetS).

Effect of high-density lipoprotein on oocyte maturation and bovine embryo development in vitro.

High-density lipoprotein (HDL) is the main lipoprotein in the follicular fluid, and it has anti-inflammatory, antioxidant and cryoprotectant properties. The anti-inflammatory potential and antioxidant potential are derived from its lipid composition, especially the apolipoprotein AI (ApoAI) and paraoxonase 1 (PON1). The aim of this study was to evaluate the effect of HDL during in vitro maturation (IVM) on oocyte maturation and early bovine embryo development. For this, cumulus-oocyte complexes (COCs) were obtained from bovine ovaries collected at a local slaughterhouse. COCs (n=2,250) were allocated into three groups (n=50 COCs/group) according to the addition of HDL protein (HDL-P) during IVM for 22hr: 0 (control), 50 and 150mg/dl. After IVM, COCs were inseminated (in vitro fertilization) and cultivated for 7days. Total cholesterol concentration, total protein, triglycerides and ApoAI concentrations on IVM medium increased proportionally to HDL-P addition. However, PON1 activity was not detected in any treatment. The addition of HDL-P did not affect nuclear maturation rate, endogenous reactive oxygen species and glutathione levels in COCs (p>0.05). The highest HDL-P concentration (150mg/dl) decreased cleavage and blastocyst rate (p<0.05). Moreover, the HDL-P 150mg/dl group had lower cellular count/blastocyst than the 50mg/dl group (p<0.05). However, the addition of HDL-P did not affect relative gene expression of evaluated genes. In conclusion, the complex HDL/ApoAI obtained from human plasma, in the absence of PON1 activity during in vitro oocyte maturation, decreased initial embryo development.

AMPK activation enhances the anti-atherogenic effects of high density lipoproteins in apoE−/− mice

HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmacological AMPK activation using A-769662, AICAR, metformin, and IMM-H007 on the atheroprotective functions of HDL in apoE-deficient (apoE−/−) mice fed with a high-fat diet. After administration, there were no changes in serum lipid levels among the groups. However, mice treated with AMPK activators showed significantly enhanced reverse cholesterol transport in vivo and in vitro. AMPK activation also increased the expression of ABCA1 and ABCG1 in macrophages and scavenger receptor class B type I and LCAT in the liver. HDL from AMPK activation mice exhibited lower HDL inflammatory index and myeloperoxidase activity and higher paraoxonase 1 activity than HDL from untreated mice, implying superior antioxidant and anti-inflammatory capacities. Pharmacological AMPK activation also induced polarization of macrophages to the M2 state and reduced plasma lipid peroxidation, inflammatory cytokine production, and atherosclerotic plaque formation in apoE−/− mice. These observations suggest that pharmacological AMPK activation enhances the anti-atherogenic properties of HDL in vivo. This likely represents a key mechanism by which AMPK activation attenuates atherosclerosis.

Abstract P118: Cardioprotective Association Between High Density Lipoprotein Cholesterol and Endothelial Function Attenuated at Lower Levels of Estradiol in Women at Midlife. The SWAN Heart Study

Objective: Growing evidence suggests that the cardioprotective effects of high density lipoproteins (HDL) may be diminished over the menopause transition. Estradiol (E2), the leading ovarian estrogen that declines substantially during the menopause transition, is considered a potent antioxidant with potential impact on lipid peroxidation and formation of reactive oxygen species that could affect HDL cardioprotective capacities. Whether the cardioprotective effects of HDL on atherosclerotic subclinical measures are apparent only in the presence of high levels of E2 in women at midlife is not clear. We hypothesized that the expected positive association between levels of high density lipoprotein cholesterol (HDL-C) and endothelial function as indexed by flow-mediated dilation (FMD) is weaker at lower levels of E2. Methods: Participants were fromthe baseline visit of the Study of Women’s Health Across the Nation (SWAN) Heart study. Women with hysterectomy and/or bilateral oophorectomy and those on hormone therapy were excluded. B-mode ultrasound images of the right brachial artery before and after deflation were obtained to estimate % change in FMD. Linear regression analyses were utilized to model the difference between log-baseline arterial diameter and log-post-deflation arterial diameter as a function of the interaction between log-E2 and HDL-C levels. To illustrate, the interaction between E2 tertiles and HDL-C was presented as well. The final model adjusted for log-baseline arterial diameter, race, study site, cycle day of blood draw, menopause status, body mass index, and diastolic blood pressure. Results were presented as % change in FMD (95% CI). Results: The study included 322 women (60% White and 40% Black) aged 50.7±2.8 years who were either in pre-/early perimenopause (63%) or late peri-/postmenopause (37%). In the final model, a significant interaction between HDL-C and log-E2 levels on %FMD was found, P value for interaction=0.01; such that a positive association between HDL-C and %FMD was only evident among women in the high E2 tertile (E2 ≥51.1 pg/ml) [%FMD (95%CI) per 1 SD increase in HDL-C: 0.93%(0.21%, 1.64%)] and that %FMD per 1 SD increase in HDL-C was significantly lower in women in the low E2 tertile (E2 &lt;21.5 pg/ml) compared to women in the high E2 tertile [%FMD difference (95%CI): low E2 tertile vs. high E2 tertile: -0.98 (-1.88, -0.07), P-value=0.03]. Conclusions: The cardioprotective association of HDL-C on endothelial function depends on levels of E2 in women at midlife, such that HDL-C may not be protective to the vascular endothelium in the setting of low endogenous E2. Our analyses should be replicated in longitudinal settings. Future studies should investigate potential mechanistic pathways by which dynamic changes in E2 levels may impact HDL composition and functionality over the menopausal transition.

Effects of High Density Lipoprotein Raising Therapies on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus, with or without Renal Impairment: The Action to Control Cardiovascular Risk in Diabetes Study

Background: The role of high density lipoprotein-raising interventions in addition to statin therapy in patients with diabetes remains controversial. Chronic kidney disease (CKD) is a strong modifier of cardiovascular (CV) outcomes. We therefore investigated the impact of CKD status at baseline on outcomes in patients with diabetes randomized to standard statin or statin plus fenofibrate treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. Methods: Among 5,464 participants in the ACCORD lipid trial, 3,554 (65%) were free of CKD at baseline, while 1,910 (35%) had mild to moderate CKD. Differences in CV outcomes during follow-up between CKD and non-CKD subgroups were examined. In addition, the effect of fenofibrate as compared to placebo on CV outcomes was examined for both subgroups. Results: All CV outcomes were 1.4-3 times higher among patients with CKD as compared to non-CKD patients. In patients with CKD, the addition of fenofibrate had no effect on any of the primary or secondary outcomes. In patients without CKD, however, the addition of fenofibrate was associated with a significant 36% reduction of CV mortality (hazards ratio [HR] 0.64; 95% CI 0.42-0.97; p value for treatment interaction <0.05) and 44% lower rate of fatal or non-fatal congestive heart failure (CHF; HR 0.56; 95% CI 0.37-0.84; p value treatment interaction <0.03). Conclusions: For patients with type 2 diabetes at high CV risk but no CKD, fenofibrate therapy added to statin reduced the CV mortality and the rate of fatal and non-fatal CHF.

Abstract 545: Differential mRNA Expression is Influenced by Apolipoprotein A-I in Order to Promote Foam Cell Regression

Atherosclerosis is a disease of both lipids and inflammatory immune cells. More specifically, elevated plasma levels of low-density lipoproteins (LDL) leads to migration of circulating monocytes into the artery wall. Lipid loaded monocyte cells subsequently proliferate in the arterial walls becoming macrophage foam cells; a hallmark of atherosclerotic lesions. A proposed mechanism of the protective effects of high-density lipoprotein (HDL) is apolipoprotein A-I (apo A-I) acting as a mediator of cholesterol efflux and subsequent foam cell regression. To better understand the biological changes stimulated by apo A-I treatment, differential expression analysis of microarray data was performed on spleen cells from apo A-I treated mice. LDL receptor null (LDLr -/- ) and LDL receptor and apo A-I null (LDLr -/- , apoA-I -/- ) mice were fed a western diet consisting of 0.2% cholesterol and 42% of calories as fat for 12 weeks. After 6 weeks of diet, a subset of mice for each genotype was subcutaneously injected with 200 micrograms of apo A-I 3 times a week for the remaining 6 weeks. The control group mice were subcutaneously injected with 200 micrograms of saline or BSA. Spleen cell RNA was isolated, purified, and analyzed for differential expression analysis using Illumina BeadArray Microarray Technology Analysis. Individual gene expression analysis for LDLr -/- , apoA-I -/- apo A-I treated mice showed 281 significantly differentially expressed genes compared to BSA treated mice. LDLr -/- A-I treated mice had 1502. Of the significant genes, 189 intersected across both genotypes. LDLr -/- , apoA-I -/- A-I mice showed 73 up-regulated and 116 down-regulated genes. Similarly, LDLr -/- A-I mice had 71 up-regulated and 118 down-regulated. One-directional Gene Set Enrichment Analysis (GSEA) of LDLr -/- , apoA-I -/- A-I mice revealed 49 significant pathways while a total of 63 were found for LDLr -/- . Of these pathways, 21 were up-regulated and 13 were down-regulated in both genotypes. Eight of the top 10 most significant up-regulated pathways in both genotypes were immune cell related. Their functions involve receptor, adhesion, and chemokine signaling. Overall, preliminary analysis suggests A-I treatment induces similar gene expression changes across different genotypes.

A Novel Anti-Inflammatory Effect for High Density Lipoprotein.

High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis.

Diabetes Mellitus and the Cardiovascular System

Diabetes mellitus (DM) is an epidemic which affects close to 100 million patients worldwide; the majority being type 2 diabetes mellitus. The rising incidence has resulted in a proportional increase in the frequency of cardiovascular disease attributable to DM, as revealed by various population-based studies. Over the past 50 years, DM has been shown to be an important and independent risk factor in the development of a variety of cardiac conditions, especially vascular disease, primarily through accelerated atherosclerosis. Diabetic neuropathy is a serious complication of DM, which leads to the impairment of cardiovascular autonomic control. Diabetic cardiac autonomic neuropathy results in heart rate abnormalities, exercise intolerance, orthostatic blood pressure abnormalities, QT interval prolongation, silent ischemia and diabetic cardiomyopathy, all of which lead to increased morbidity and mortality related to diabetes. This conditions remains difficult to diagnose and treat, requiring a multifaceted approach. Inflammation appears to play a central role in accelerating many of the injurious effects of DM on the cardiovascular system. Expression of specific inflammatory markers has been directly linked to some of the known harmful effects of DM on the cardiovascular system, in addition to indirectly potentiating the deleterious effects of other major cardiovascular disease risk factors. Hyperglycemia results in increased intracellular glucose which triggers several pro-inflammatory reactions leading to the production of harmful free radicals and the formation of advanced glycation end products. These have been linked to the development of diabetic atherogenic dyslipidemia, in addition to glycation and loss of the protective effect of high density lipoproteins in diabetic subjects, thereby worsening the atherosclerotic burden in DM. Addressing hyperglycemia, therefore, is only one of many vital components in the treatment of diabetes. Traditional risk factors for heart disease and stroke tend to be further potentiated by the presence of DM, however, even after adequate control of hyperglycemia. Clinical evidence and major clinical guidelines address this conundrum by pointing out unmet needs of adequate cardiovascular protection, and call for aggressive control of risk factors in the diabetic population. J Endocrinol Metab. 2015;5(6):313-320 doi: http://dx.doi.org/10.14740/jem324e

The association of HDL-apoCIII with coronary heart disease and the effect of statin treatment on it.

BackgroundApolipoprotein CIII (apoCIII) is considered to impair the anti-atherogenic effect of high density lipoprotein (HDL) in coronary heart disease (CHD) patients, and apoCIII content in HDL (HDL-apoCIII) predicts CHD more accurately. However, the relationship between HDL-apoCIII and CHD, and the effect of statin treatment on HDL-apoCIII are still unclear. The aims of the study are to establish the association of HDL-apoCIII with CHD, and investigate the effect of statin treatment on HDL-apoCIII in CHD patients.MethodsWe conducted a hospital-based observational study. Totally 80 non-CHD patients and 120 CHD patients without statin treatment were previously enrolled in this study. All the CHD patients received statin treatment, and 63 of them were followed after 3 months of regular statin treatment. HDL sample of each patient was isolated by density gradient ultracentrifugation from fasting venous plasma, and HDL-apoCIII of each patient was measured by ELISA method.ResultsHDL-apoCIII was significantly higher in CHD patients than non-CHD patients (p < 0.05), and it was still an independent predictor of CHD after adjusting for other factors. Total plasma apoCIII, especially HDL-apoCIII was significantly elevated after statin treatment in CHD patients, whereas total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and apolipoprotein B (apoB) were decreased significantly (p < 0.05). Compared with CHD patients without diabetes mellitus (DM), the effect of statin treatment on apoCIII markers was minor in CHD patients with DM. And HDL-apoCIII correlated with plasma TG significantly in non-CHD and CHD patients (p < 0.05), but the correlation in CHD patients did not exist after statin treatment (p > 0.05).ConclusionsHDL-apoCIII has a significant and positive association with CHD. Although conventional atherogenic lipid markers have a significantly decrease in CHD patients after statin treatment, HDL-apoCIII has a further elevation at the same time.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0129-8) contains supplementary material, which is available to authorized users.