Oxidative Damage Markers Are Significantly Associated with the Carotid Artery Intima-Media Thickness after Controlling for Conventional Risk Factors of Atherosclerosis in Men

Background

This study aimed to assess the association between oxidative damage markers and carotid artery intima-media thickness (CIMT) after controlling for conventional risk factors of atherosclerosis in multiple logistic regression models.

Methods and Findings

Fifty-one case male participants (CIMT ≥ 0.9 mm) were enrolled during their visits to Korean Genomic Rural Cohort Study of Wonju centers between May 1 and August 31, 2011, along with 51 control participants (CIMT < 0.9 mm) selected using frequency matching by age group. The levels of oxidative damage markers, 8-hydroxy-2′-deoxyquuanosine (8-OHdG), malondialdehyde (MDA), and 8-iso-prostaglandin F2α (Isoprostane), were measured. Conditional logistic regression models were used to evaluate relative relationships between the oxidative damage markers and the risk of high CIMT.

Results

The markers of oxidative lipid (Isoprostane and MDA) and DNA (8-OHdG) damage were associated with CIMT after controlling for the conventional risk factors, including age, low density lipoprotein, body mass index, smoking history, alcohol consumption, and metabolic syndrome (ORs [95% CI] for Isoprostane: 3^rd tertile, 8.47 [2.59-27.67]; for MDA: 3^rd tertile, 8.47 [2.59-27.67]; for 8-OHdG: 3^rd tertile, 5.58 [1.79-17.33]). When all the oxidative damage markers were incorporated in the same logistic regression model, only Isoprostanewas significantly related to CIMT (OR [95% CI]: 4.22 [1.31-13.53] in 2^nd tertile and 14.21 [3.34-60.56] in 3^rd tertile).

Conclusions

In this nested case-control study, the oxidative damage markers of lipid and DNA were associated with CIMT even after controlling for the conventional risk factors of cardiovascular diseases.     

Inverse Association of Serum Vitamin D in Relation to Carotid Intima-Media Thickness in Chinese Postmenopausal Women

Objective

This study aimed to investigate the relationship between serum vitamin D level and carotid intima-media thickness (C-IMT) in Chinese postmenopausal women.

Methods

Nine hundred and twenty six Chinese postmenopausal women without carotid artery plaque or history of cardiovascular disease were selected for analysis. Measurements of serum 25 hydroxyvitamin D₃ (25(OH)D₃) concentration and C-IMT were made by electrochemiluminescence immunoassay and B-mode ultrasound, respectively. Trend analysis was conducted according to tertiles of C-IMT.

Results

The median serum 25(OH)D₃ level was 11.03 ng/mL, with an interquartile range of 8.22–14.70. A decreasing trend of serum 25(OH)D₃ level was accompanied by increased C-IMT tertiles (P for trend = 0.001). Correlation analysis found an inverse relationship between serum 25(OH)D₃ level and C-IMT (r = –0.113, P = 0.001). After adjustment for confounding factors, multiple regression analysis showed that serum 25(OH)D₃ level independently and negatively associated with C-IMT (Standard β = –0.112, P < 0.001). Moreover, the inverse correlation of serum 25(OH)D₃ with C-IMT was also found in a subgroup of women with normal glucose tolerance, blood pressure and body mass index, and without undergoing lipid-lowering therapy (standard β = –0.140, P = 0.018).

Conclusions

Serum 25(OH)D₃ level was inversely correlated with C-IMT in Chinese postmenopausal women.     

Circulating Lipocalin-2 and Retinol-Binding Protein 4 Are Associated with Intima-Media Thickness and Subclinical Atherosclerosis in Patients with Type 2 Diabetes

Background

The lipocalin family proteins, including lipocalin-2 and retinol-binding protein 4 (RBP4), are adipokines closely associated with obesity-related metabolic disorders. In this study, we evaluated the association of serum lipocalin-2 and RBP4 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.

Methods and Results

Serum levels of lipocalin-2 and RBP4 were measured in 284 type 2 diabetic patients. Subclinical atherosclerosis was assessed by IMT at carotid, femoral and iliac arteries with ultrasound. Patients with subclinical atherosclerosis showed significantly higher circulating concentrations of lipocalin-2 and RBP4 when compared to those without [112.9 (86.4 to 202.1) µg/L versus 77.2(55.0–150.4) µg/L, 37.1(32.3–40.8) mg/L versus 23.2(20.1–29.2) mg/L, respectively; P = 0.002, P<0.001, respectively]. Moreover, positive correlations were observed between carotid IMT and lipocalin-2 (r = 0.170, P = 0.018) or RBP4 (r = 0.132, P = 0.040), femoral IMT and lipocalin-2 (r = 0.160, P = 0.027), as well as between iliac IMT and RBP4 (r = 0.241, P<0.001). Multiple logistic regression analysis further demonstrated that these two adipokines were independent risk factors for subclinical atherosclerosis in type 2 diabetes.

Conclusion

Circulating levels of lipocalin-2 and RBP4 are positively correlated with carotid IMT and subclinical atherosclerosis in type 2 diabetes, which suggests a potential role of these two lipid-binding chaperones in the pathogenesis of vascular complications of diabetes.     

Mildly Elevated Serum Bilirubin Levels Are Negatively Associated with Carotid Atherosclerosis among Elderly Persons

Serum bilirubin may have a beneficial role in preventing oxidative changes in atherosclerosis. Limited information is available on whether serum total bilirubin is an independent confounding factor for carotid atherosclerosis {for example, intima-media thickness (IMT), plaque} measured noninvasively by B-mode ultrasonography only among elderly persons. The study subjects were 325 men aged 79±8 (mean ± standard deviation) years and 509 women aged 81±8 years that were enrolled consecutively from patients aged ≥60 years in the medical department. Carotid IMT and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that in men age (β = 0.199, p = 0.002), smoking status (β = 0.154, p = 0.006), GGT (β = -0.139, p = 0.039), and GGT (β = -0.133, p = 0.022) were significantly and independently associated with carotid IMT, and in women age (β = 0.186, p<0.001), systolic blood pressure (β = 0.104, p = 0.046), diastolic blood pressure (β = -0.148, p = 0.004), prevalence of antihypertensive medication (β = 0.126, p = 0.004), fasting plasma glucose (β = 0.135, p = 0.003), GGT (β = -0.104, p = 0.032), estimated glomerular filtration rate, serum bilirubin (β = -0.119, p = 0.006), and prevalence of cardiovascular disease (CVD) (β = 0.103, p = 0.017) were also independently associated with carotid IMT. The odds ratios (ORs) {95% confidence interval (CI)} of increasing serum bilirubin category were negatively associated with carotid IMT ≥1.0 mm and plaque in both genders. Compared to subjects with a serum bilirubin of Quartile-1, the multivariate-OR (95% CI) of carotid plaque was 0.25 (0.11–0.57) in the Quartile-4 male group, and 0.41 (0.21–0.78) in the Quartile-2 female group, 0.51 (0.26–0.98) in the Quartile-3 female group, and 0.46 (0.24–0.89) in the Quartile-4 female group. Our data demonstrated an independently negative association between serum bilirubin and carotid atherosclerosis in both genders.     

Impact of Multiple Cardiovascular Risk Factors on Carotid Intima-Media Thickness and Elasticity

Background

Carotid intima-media thickness (IMT) and elasticity have been shown to be independent predictors of cardiovascular disease (CVD). Cardiovascular risk factors (CVRFs) includes hypertension, dyslipidemia, diabetes, overweight and smoking. The objective was to investigate whether the clustering of three or more components of CVRFs has a greater impact on carotid IMT and elasticity than individual components of CVRFs.

Methods

One hundred and seventy-three participants without clinical CVD were classified as the multiple CVRFs patients with three or more CVRFs (n  = 55) and control group with two or less CVRFs (n  = 118). Carotid IMT and elastic modulus were measured by B-mode ultrasound and vessel texture matching method (VTMM), respectively.

Results

The multiple CVRFs conferred a disproportionate increase in carotid IMT (43%, p<0.0001) and elastic modulus (60%, p<0.0001), compared with control group. Multiple regression models, which included age, gender, as well as each individual component of CVRFs as continuous variables, showed that multiple CVRFs was an independent determinant of both IMT (p  = 0.042) and elasticity (p  = 0.008). In the analysis of variance adjusted with age, subjects with single, double, and multiple CVRFs, increased by 8.1%, 42.2%, and 66% for IMT, 54.6%, 94.3%, and 125.2% for elastic modulus, respectively, compared to subjects without CVRFs.

Conclusions

The clustering of multiple CVRFs has a greater impact on carotid IMT and elasticity than individual components of CVRFs. This suggests that the components of CVRFs interact to synergistically impact carotid IMT and elasticity.     

Urinary miR-29 Correlates with Albuminuria and Carotid Intima-Media Thickness in Type 2 Diabetes Patients

Background

Cell-free microRNAs stably and abundantly exist in body fluids and emerging evidence suggests cell-free microRNAs as novel and non-invasive disease biomarker. Deregulation of miR-29 is involved in the pathogenesis of diabetic nephropathy and insulin resistance thus may be implicated in diabetic vascular complication. Therefore, we investigated the possibility of urinary miR-29 as biomarker for diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.

Methods

83 patients with type 2 diabetes were enrolled in this study, miR-29a, miR-29b and miR-29c levels in urine supernatant was determined by TaqMan qRT-PCR, and a synthetic cel-miR-39 was added to the urine as a spike-in control before miRNAs extraction. Urinary albumin excretion rate and urine albumin/creatinine ratio, funduscopy and carotid ultrasound were used for evaluation of diabetic vascular complication. The laboratory parameters indicating blood glucose level, renal function and serum lipids were also collected.

Results

Patients with albuminuria (n = 42, age 60.62±12.00yrs) showed significantly higher comorbidity of diabetic retinopathy (p = 0.015) and higher levels of urinary miR-29a (p = 0.035) compared with those with normoalbuminuria (n = 41, age 58.54±14.40yrs). There was no significant difference in urinary miR-29b (p = 0.148) or miR-29c level (p = 0.321) between groups. Urinary albumin excretion rate significantly correlated with urinary miR-29a level (r = 0.286, p = 0.016), while urinary miR-29b significantly correlated with carotid intima-media thickness (cIMT) (r = 0.286, p = 0.046).

Conclusion

Urinary miR-29a correlated with albuminuria while urinary miR-29b correlated with carotid intima-media thickness (cIMT) in patients with type 2 diabetes. Therefore, they may have the potential to serve as alternative biomarker for diabetic nephropathy and atherosclerosis in type 2 diabetes.     

Human Apolipoprotein A-I Is Associated with Dengue Virus and Enhances Virus Infection through SR-BI

Diseases caused by dengue virus (DV) infection vary in severity, with symptoms ranging from mild fever to life threatening dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS). Clinical studies have shown that significant decrease in the level of lipoproteins is correlated with severe illness in DHF/DSS patients. Available evidence also indicates that lipoproteins including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) are able to facilitate cell entry of HCV or other flaviviruses via corresponding lipoprotein receptors. In this study, we found that pre-incubation of DV with human serum leads to an enhanced DV infectivity in various types of cells. Such enhancement could be due to interactions between serum components and DV particles. Through co-immunoprecipitation we revealed that apolipoprotein A-I (ApoA-I), the major protein component in HDL, is associated with DV particles and is able to promote DV infection. Based on that observation, we further found that siRNA knockdown of the scavenger receptor class B type I (SR-BI), the cell receptor of ApoA-I, abolished the activity of ApoA-I in enhancement of DV infection. This suggests that ApoA-I bridges DV particles and cell receptor SR-BI and facilitates entry of DV into cells. FACS analysis of cell surface dengue antigen after virus absorption further confirmed that ApoA-I enhances DV infection via promoting initial attachment of the virus to cells. These findings illustrate a novel entry route of DV into cells, which may provide insights into the functional importance of lipoproteins in dengue pathogenesis.     

Apolipoprotein A-I Modulates Processes Associated with Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

Apolipoprotein A-I (apoA-I) is the main protein of high-density lipoprotein (HDL). We investigated the involvement of apoA-I in diet-induced accumulation of triglycerides in hepatocytes and its potential role in the treatment of nonalcoholic fatty liver disease (NAFLD). ApoA-I–deficient (apoA-I^−/−) mice showed increased diet-induced hepatic triglyceride deposition and disturbed hepatic histology while they exhibited reduced glucose tolerance and insulin sensitivity. Quantification of FASN (fatty acid synthase 1), DGAT-1 (diacylglycerol O-acyltransferase 1), and PPARγ (peroxisome proliferator-activated receptor γ) mRNA expression suggested that the increased hepatic triglyceride content of the apoA-I^−/− mice was not due to de novo synthesis of triglycerides. Similarly, metabolic profiling did not reveal differences in the energy expenditure between the two mouse groups. However, apoA-I^−/− mice exhibited enhanced intestinal absorption of dietary triglycerides (3.6 ± 0.5 mg/dL/min for apoA-I^−/− versus 2.0 ± 0.7 mg/dL/min for C57BL/6 mice, P < 0.05), accelerated clearance of postprandial triglycerides and a reduced rate of hepatic very low density lipoprotein (VLDL) triglyceride secretion (9.8 ± 1.1 mg/dL/min for apoA-I^−/− versus 12.5 ± 1.3 mg/dL/min for C57BL/6 mice, P < 0.05). In agreement with these findings, adenovirus-mediated gene transfer of apoA-I_Milano in apoA-I^−/− mice fed a Western-type diet for 12 wks resulted in a significant reduction in hepatic triglyceride content and an improvement of hepatic histology and architecture. Our data extend the current knowledge on the functions of apoA-I, indicating that in addition to its well-established properties in atheroprotection, it is also an important modulator of processes associated with diet-induced hepatic lipid deposition and NAFLD development in mice. Our findings raise the interesting possibility that expression of therapeutic forms of apoA-I by gene therapy approaches may have a beneficial effect on NAFLD.     

Autophagic Marker MAP1LC3B Expression Levels Are Associated with Carotid Atherosclerosis Symptomatology

Objectives

The mechanism by which atheroma plaque becomes unstable is not completely understood to date but analysis of differentially expressed genes in stable versus unstable plaques may provide clues. This will be crucial toward disclosing the mechanistic basis of plaque instability, and may help to identify prognostic biomarkers for ischaemic events. The objective of our study was to identify differences in expression levels of 59 selected genes between symptomatic patients (unstable plaques) and asymptomatic patients (stable plaques).

Methods

80 carotid plaques obtained by carotid endarterectomy and classified as symptomatic (>70% stenosis) or asymptomatic (>80% stenosis) were used in this study. The expression levels of 59 genes were quantified by qPCR on RNA extracted from the carotid plaques obtained by endarterectomy and analyzed by means of various bioinformatic tools.

Results

Several genes associated with autophagy pathways displayed differential expression levels between asymptomatic and symptomatic (i.e. MAP1LC3B, RAB24, EVA1A). In particular, mRNA levels of MAP1LC3B, an autophagic marker, showed a 5−fold decrease in symptomatic samples, which was confirmed in protein blots. Immune system−related factors and endoplasmic reticulum-associated markers (i.e. ERP27, ITPR1, ERO1LB, TIMP1, IL12B) emerged as differently expressed genes between asymptomatic and symptomatic patients.

Conclusions

Carotid atherosclerotic plaques in which MAP1LC3B is underexpressed would not be able to benefit from MAP1LC3B−associated autophagy. This may lead to accumulation of dead cells at lesion site with subsequent plaque destabilization leading to cerebrovascular events. Identified biomarkers and network interactions may represent novel targets for development of treatments against plaque destabilization and thus for the prevention of cerebrovascular events.     

Apolipoprotein B, apolipoprotein A-I, insulin resistance and the metabolic syndrome

PURPOSE OF REVIEW: The goal of identifying subjects with metabolic syndrome is to detect those at higher risk of developing cardiovascular disease. Evidence continues to accumulate as to the superiority of apolipoprotein B and apolipoprotein A-I over the conventional lipoprotein lipids as markers of vascular risk. It would seem reasonable, therefore, to redefine the dyslipidemia of the metabolic syndrome incorporating apolipoproteins. Therefore, our objective is to elucidate how apolipoprotein B and apolipoprotein A-I amplify evidence of the interactions amongst metabolic syndrome, insulin resistance, abdominal obesity, and vascular risk. RECENT FINDINGS: In several large epidemiological studies, including the NHANES III database, apolipoprotein B/apolipoprotein A-I ratio was tightly linked to the metabolic syndrome and each of its components, the descending order being: low HDL cholesterol, high triglyceride, high waist circumference, high glucose, and high blood pressure. Moreover, apolipoprotein B associates more closely with inflammatory markers and insulin resistance than triglyceride and all cholesterol markers. Yet despite close association of the apolipoprotein B/apolipoprotein A-I ratio to metabolic syndrome, both are independent predictors of future myocardial infarction. SUMMARY: We believe that the dyslipidemia of the metabolic syndrome should be redefined to include apolipoprotein B and apolipoprotein A-I.     

血清脂联素、载脂蛋白B/A1比值与颈总动脉内——中膜厚度和冠脉病变的相关性研究

目的:探讨血清脂联素、栽脂蛋白B/我脂蛋白A1比值与颈动脉内中膜厚度(IMT)的相关性,为冠心病的早期诊断提供简便、客观的指标.方法:入选经冠状动脉造影证实的冠心痛患者81例,其中单支病变组21例,多支病变组60例,另选冠状动脉造影正常者17例为对照组.采用高频超声探测双侧颈总动脉内中膜厚度(IMT),以及测定血清脂联素、载脂蛋白B/载脂蛋白A1水平,分析三者之间的相关性以及和冠心病的关系.结果:血清脂联素与颈动脉内中膜厚度呈负相关,载脂蛋白B/栽脂蛋白A1比值与颈动脉内中膜厚度呈正相关.与正常对照组相比,冠状动脉单支或多支病变组血清脂联素水平降低,而栽脂蛋白B/载脂蛋白A1比值、颈动脉内中膜厚度明显增高.结论:血清脂联素、载脂蛋白B/载脂蛋白A1比值与颈动脉内中膜厚度对于冠心痛的诊断有重要的预测价值.     

2型糖尿病患者糖化血红蛋白水平与颈动脉内-中膜厚度的相关性

目的:分析2型糖尿病(T2DM)患者糖化血红蛋白(Hb A1c)水平与颈动脉内-中膜厚度(CIMT)的相关性。方法:选择在我院内分泌科住院的T2DM患者328名,对入组患者进行Hb A1c、血生化指标检测以及CIMT测量等。根据CIMT值分为CIMT正常组(0.9 mm)和CIMT增厚组(0.9 mm),并对CIMT的相关危险因素进行多因素Logistic回归分析。结果:(1)328名T2DM患者中,CIMT正常154例,CIMT增厚174例;(2)Pearson相关分析显示,总胆固醇(TC)、Hb A1c水平与IMT值呈正相关(P0.05)。(3)单因素分析示,CIMT正常组和CIMT增厚组两组间年龄(t=4.132,P=0.041)、收缩压(t=8.456,P0.01)、Hb A1c≥9.0%(x~2=9.912,P0.01)、总胆固醇(t=5.549,P=0.018)、甘油三酯(t=6.592,P=0.008)、尿酸(t=9.618,P0.01)、空腹血糖(t=4.592,P=0.037)间差异有统计学意义;(4)多因素Logistic回归分析示,年龄、Hb A1c≥9%、收缩压、总胆固醇是T2DM患者CIMT增厚的独立危险因素(P0.05)。结论:Hb A1c与CIMT增厚明显相关;且Hb A1c≥9%是CIMT增厚的独立危险因素。     

Traditional Risk Factors Are More Relevant than HIV-Specific Ones for Carotid Intima-Media Thickness (cIMT) in a Brazilian Cohort of HIV-Infected Patients

BackgroundCombination antiretroviral therapy (cART) had a dramatic impact on the mortality profile in human immunodeficiency virus (HIV) infected individuals and increased their life-expectancy. Conditions associated with the aging process have been diagnosed more frequently among HIV-infected patients, particularly, cardiovascular diseases.MethodsPatients followed in the Instituto de Pesquisa Clínica Evandro Chagas (IPEC) prospective cohort in Rio de Janeiro were submitted to the general procedures from the Brazilian Longitudinal Study of Adult Health, comprising several anthropometric, laboratory and imaging data. Carotid intima-media thickness (cIMT) was measured by ultrasonography, following the Mannheim protocol. Linear regression and proportional odds models were used to compare groups and covariables in respect to cIMT. The best model was chosen with the adaptive lasso procedure.ResultsA valid cIMT exam was available for 591 patients. Median cIMT was significantly larger for men than women (0.56mm vs. 0.53mm; p = 0.002; overall = 0.54mm). In univariable linear regression analysis, both traditional risk factors for cardiovascular diseases (CVD) and HIV-specific characteristics were significantly associated with cIMT values, but the best multivariable model chosen included only traditional characteristics. Hypertension presented the strongest association with higher cIMT terciles (OR = 2.51; 95%CI = 1.69–3.73), followed by current smoking (OR = 1,82; 95%CI = 1.19–2.79), family history of acute myocardial infarction or stroke (OR = 1.60; 95%CI = 1.10–2.32) and age (OR per year = 1.12; 95%CI = 1.10–1.14).ConclusionsOur results show that traditional cardiovascular disease (CVD) risk factors are the major players in determining increased cIMT among HIV infected patients in Brazil. This finding reinforces the need for thorough assessment of those risk factors in these patients to guarantee the incidence of CVD events remain under control.     

Comparison of Carotid Intima-Media Thickness in Children and Adults With and Without Obesity: A Hysteresis Model

ObjectiveTo describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in the pediatric and adult groups.MethodsA quasi-experimental study with fixed factor analysis of age (children aged 8-12 years, n = 73; adults aged 21-45 years, n = 82) and obesity (yes, n = 76; no, n = 79) was conducted to analyze the effect on the c-IMT and Matsuda insulin sensitivity index values. This quasi-experimental design was analyzed with robust regression modeling.ResultsThe additive effect of obesity, independent of age, was evident in the case of the c-IMT values. There was no interaction effect, but a significant difference between participants with normal weight and those with obesity was found (P < .0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda insulin sensitivity index values. A linear function fit as R², and the cubic function estimated parameters like a polynomial model.ConclusionThis practical study design showed that children with obesity displayed the same levels of carotid intima-media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and may predict chronic cardiometabolic events during early adulthood.     

阿托伐他汀钙对无动脉硬化原发性高血压患者血脂和颈动脉内膜中层厚度的影响

目的:研究阿托伐他汀钙对无动脉硬化原发性高血压患者血脂和颈动脉内膜中层厚度(cal MT)的影响。方法:选取2013年7月到2014年7月我院收治的无动脉硬化原发性高血压患者100例,按照随机数字表法将患者分为研究组和对照组,每组50例,对照组给予常规治疗,研究组在对照组的基础上给予阿托伐他汀钙治疗,治疗时间均为6个月。比较治疗前、治疗后两组血脂、血压以及cal MT。结果:研究组治疗后总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)显著降低,高密度脂蛋白胆固醇(HDL-C)显著增高,且显著优于对照组治疗后,比较差异具有统计学意义(P0.05);两组治疗后血压均显著低于治疗前,比较差异具有统计学意义(P0.05),且治疗后研究组显著优于对照组,比较差异具有统计学意义(P0.05);治疗后研究组cal MT显著优于治疗前,且优于对照组,比较差异具有统计学意义(P0.05)。结论:阿托伐他汀钙治疗无动脉硬化原发性高血压能显著改善患者血脂水平,降低其cal MT,对预防患者动脉粥样硬化具有重要意义。     

Effect of Feeding Xenobiotics on Serum High Density Lipoprotein and Apolipoprotein A-I in Rats

The effects on serum cholesterol level were examined in rats fed on various xenobiotics. The hypercholesterolemia induced by polychlorinated biphenyls (PCB) was characterized in rats, from which lipoproteins were isolated by ultracentrifugation. A dietary addition of 0.03% PCB, 0.3% chloretone, 0.1% aminopyrine, or 0.2% 2,6-di-tert-butyl-p-cresol (BHT) resulted in a significant increase in serum cholesterol, although the chemical structure of each of these xenobiotics was different. The serum cholesterol level was markedly increased by one month of PCB feeding, the effect of PCB on the serum phospholipid level being similar. The serum triglyceride level transiently increased within 7 days of feeding with PCB diet. PCB feeding resulted in the elevation of all lipoproteins, including VLDL, LDL, HDL₁, and HDL₂, a marked increase being observed in HDI₁. Both HDL₁ and HDL₂ isolated from PCB-treated rats contained more apolipoprotein A-I (apo A-I) and less apo E than normal. VLDL isolated from PCB-treated rats had more cholesterol and apo E, but less apo C than that of the control animals. These data demonstrate that PCB feeding resulted in increased VLDL rich in cholesterol and apo E, and increased HDL rich in apo A-I. This experimentally induced hypercholesterolemia resulting in apo A-I-rich HDL would be a useful model for investigating the metabolism of apo-A-I and HDL.     

Apolipoprotein E Gene Polymorphisms Are Associated with Primary Hyperuricemia in a Chinese Population

Objective

Primary hyperuricemia, an excess of uric acid in the blood, is a major public health problem. In addition to the morbidity that is attributable to gout, hyperuricemia is also associated with metabolic syndrome, hypertension, and cardiovascular disease. This study aims to assess the genetic associations between Apolipoprotein E (APOE) polymorphisms and hyperuricemia in a Chinese population.

Methods

A total of 770 subjects (356 hyperuricemic cases and 414 normouricemic controls) were recruited from the Ningxia Hui Autonomous Region, China. A physical examination was performed and fasting blood was collected for biochemical tests, including determination of the levels of serum lipid, creatinine, and uric acid. Multi-ARMS PCR was applied to determine the APOE genotypes, followed by an investigation of the distribution of APOE genotypes and alleles frequencies in the controls and cases.

Results

The frequencies of the APOE-ε2ε3 genotype (17.70% vs. 10.39%, P = 0.003) and the APOE-ε2 allele (10.53% vs. 5.80%, P = 0.001) were significantly higher in the hyperuricemic group than in the normouricemic group. Furthermore, male cases were more likely to have the APOE-ε2ε3 genotype and APOE-ε2 allele, compared with male controls. In both Han and Hui subjects, cases were more likely to have the APOE-ε2ε3 genotype and the APOE-ε2 allele compared with controls. Furthermore, multivariate logistic regression showed that carriers of the APOE-ε2ε3 genotype (P = 0.001, OR = 2.194) and the ε2 allele (P = 0.001, OR = 2.099) were significantly more likely to experience hyperuricemia than carriers of the ε3/ε3 genotype and the ε3 allele after adjustment for sex, body mass index (BMI), diastolic blood pressure (DBP), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), creatinine (Cr) and fasting blood glucose(FBG).

Conclusions

The APOE-ε2ε3 genotype and the APOE-ε2 allele are associated with serum uric acid levels in Chinese subjects, indicating that individuals carrying the APOE-ε2 allele have a higher risk of hyperuricemia than non-carriers.     

Osteoprotegerin,Pericytes and Bone-Like Vascular Calcification Are Associated with Carotid Plaque Stability

Background and Purpose

Vascular calcification, recapitulating bone formation, has a profound impact on plaque stability. The aim of the present study was to determine the influence of bone-like vascular calcification (named osteoid metaplasia = OM) and of osteoprotegerin on plaque stability.

Methods

Tissue from carotid endarterectomies were analysed for the presence of calcification and signs of vulnerability according to AHA grading system. Osteoprotegerin (OPG), pericytes and endothelial cells were sought using immuno-histochemistry. Symptoms and preoperative imaging findings (CT-scan, MRI and Doppler-scan) were analyzed. Human pericytes were cultured to evaluate their ability to secrete OPG and to influence mineralization in the plaque.

Results

Seventy-three carotid plaques (49 asymptomatic and 24 symptomatic) were harvested. A significantly higher presence of OM (18.4% vs 0%, p<0.01), OPG (10.2% of ROI vs 3.4% of ROI, p<0.05) and pericytes (19% of ROI vs 3.8% of ROI, p<0.05) were noted in asymptomatic compared to symptomatic plaques. Consistently, circulating OPG levels were higher in the plasma of asymptomatic patients (3.2 ng/mL vs 2.5 ng/mL, p = 0.05). In vitro, human vascular pericytes secreted considerable amounts of OPG and underwent osteoblastic differentiation. Pericytes also inhibited the osteoclastic differentiation of CD14+ cells through their secretion of OPG.

Conclusions

OPG (intraplaque an plasmatic) and OM are associated with carotid plaque stability. Pericytes may be involved in the secretion of intraplaque OPG and in the formation of OM.     

Impact of Cardiovascular Risk Factors on Carotid Intima-Media Thickness and Degree of Severity: A Cross-Sectional Study

Objective

Age, hypertension, dyslipidemia and diabetes are common cardiovascular risk factors (CVRFs) that contribute to the development of atherosclerosis in cardiovascular system including carotid artery disease. However, the impact of these risk factors on the increased carotid intima-media thickness (cIMT) and degree of carotid severity remains to be further clarified. This study aims to evaluate the relationship between CVRFs and degree of carotid severity and cIMT in high-risk subjects.

Methods

Four thousand and three hundred ninety-four subjects with one or more risk factors were retrospectively reviewed in this study. Patients were divided into different groups based on age, the type and quantity of CVRFs. cIMT and degree of carotid artery stenosis were measured and analyzed based on carotid ultrasound imaging with findings compared to the CVRFs to determine the correlation between these variables.

Results

Aging was significantly associated with degree of severity (P < 0.05) and cIMT was significantly increased with age (P < 0.05). Individual CVRF analysis shows that hypertension was more related to the degree of severity than dyslipidemia and diabetes with corresponding abnormal cIMT rates being 79.39%, 72.98% and 32.37%, respectively. The prevalence of carotid atherosclerosis were 20.06%, 22.88% and 28.63%, respectively corresponding to patients with zero, one and more than one chronic diseases. The percentage of abnormal cIMT in hypertensive patient group with dyslipidemia is significantly higher than the other groups (P< 0.05).

Conclusions

This study shows a direct correlation between the degree of carotid severity and cIMT and cardiovascular risk factors, especially with age and hypertension. Carotid atherosclerosis is closely related to the number of cardiovascular risk factors.