Evaluation of carotid intima media thickness in children with idiopathic nephrotic syndrome

AimAim of the study was to determine if carotid intima media thickness in children with idiopathic nephrotic syndrome is greater than in healthy subjects, and to assess whether carotid intima media thickness in children with nephrotic syndrome is associated with clinical (including disease duration, cumulative dose of steroids, number of relapses) and biochemical parameters.MethodsA cross-sectional study included 40 patients with nephrotic syndrome (mean age 11.7 ± 4.7 years). Steroid dependent nephrotic syndrome was established in 32 patients (80%), while 8 (20%) had steroid resistant nephrotic syndrome. Control group consisted of 20 age and gender matched healthy children. Blood pressure based on 24-h ambulatory blood pressure monitoring (ABPM), carotid intima media thickness, fasting glucose, insulin, HbA1c, lipid concentrations were measured in all children.ResultsA significant difference was detected in carotid intima media thickness values (P = 0.036). Children with nephrotic syndrome had significantly greater carotid intima media thickness compared with healthy children (0.42 ± 0.06 and 0.38 ± 0.03 mm). Carotid intima-media thickness was positively associated with duration of nephrotic syndrome (r = 0.45; P = 0.004), body mass index (r = 0.48; P = 0.002), daytime systolic blood pressure (r = 0.46; P = 0.003) and night-time systolic blood pressure (r = 0.52; P = 0.001). Multiple linear regression showed that duration of nephrotic syndrome was the only independent predictor of carotid intima media thickness in children with nephrotic syndrome (R² = 0.244; β=0.327; P = 0.037).ConclusionThe findings of the present study suggest subclinical vascular damage in patients with nephrotic syndrome. Duration of nephrotic syndrome was the only independent predictor of carotid intima media thickness.     

Adipophilin通过PI3K/Akt通路促进细胞内脂质蓄积

目的:探讨adipophilin促进细胞内脂质蓄积的可能机制,为动脉粥样硬化的防治提供参考。方法:分别通过q PCR、Western blot和油红O染色观察氧化型低密度脂蛋白(ox LDL)处理RAW264.7细胞不同时间后,细胞内Akt、p-Akt和adipophilin的蛋白水平及脂质蓄积情况;并检测PI3K/Akt抑制剂LY294002处理后,上述指标的变化;HEK293细胞过表达adipophilin后,检测Akt的活性;并用免疫共沉淀实验检测adipophilin与Akt之间的相互作用。结果:ox LDL处理细胞后,随着时间的延长,脂滴增多,Akt被活化,adipophilin表达增加,而LY294002处理则可抑制上述变化;过表达adipophilin后,p-Akt水平增高,但adipophilin与Akt之间未见直接相互作用。结论:Adipophilin可通过PI3K/Akt途径促进细胞内脂质蓄积,但可能不是通过直接相互关系发挥作用的。     

HSP22在高脂致动脉粥样硬化病变中的作用及对他汀干预的影响

目的:研究热休克蛋白22(heat shock protein 22,HSP22)在高脂饮食诱导的小鼠动脉粥样硬化(atherosclerosis,AS)病变中的作用,及其对阿托伐他汀(atorvastatin,Ator)干预的影响。方法:8~9周龄Apo E~(-/-)和HSP22~(-/-)Apo E~(-/-)和HSP22+Apo E~(-/-)雄性小鼠各18只,每种小鼠分为2个亚组,分别为对照组与他汀干预组(Ator组),HSP22~(-/-)组(KO组)与HSP22~(-/-)他汀干预组(KO+Ator组)及HSP22~+组(Tg组)与HSP22~+他汀干预组(Tg+Ator组),各干预组从第5周开始给予Ator(10 mg·kg~(-1)·d~(-1))干预,各对照组给予等量生理盐水,共饲养13周。采用油红O及苏木精-伊红(hematoxylin-eosin,HE)染色法观察AS病变程度,免疫组化法、Western blot法和ELISA法检测主动脉和血清中HSP22、NF-κB、eNOS、ICAM-1及IL-6的表达。结果:油红O及HE染色示Tg组主动脉斑块相对面积低于KO组(P0.05)。KO组的血清和主动脉中HSP22的蛋白表达显著低于对照组和Tg组,对照组显著低于Tg组。Tg组及对照组的主动脉eNOS蛋白的表达显著高于KO组。对照组的主动脉NF-κB及ICAM-1蛋白表达较KO组显著降低,较Tg组显著升高。对照组、KO组及Tg组血清IL-6水平的差异无统计学显著性。结论:HSP22基因缺失可上调NF-κB和ICAM-1的表达,降低eNOS的表达,加速AS的进展;HSP22基因过表达可降低NF-κB和ICAM-1的表达,从而改善AS。HSP22基因缺失部分限制了他汀下调NF-κB和ICAM-1及上调eNOS表达的作用;其过表达可促进他汀下调ICAM-1表达,进一步改善AS。     

Potential of anti-inflammatory agents for treatment of atherosclerosis

Chronic inflammation is a central pathogenic mechanism of atherosclerosis induction and progression. Vascular inflammation is associated with accelerated onset of late atherosclerosis complications. Atherosclerosis-related inflammation is mediated by a complex cocktail of pro-inflammatory cytokines, chemokines, bioactive lipids, and adhesion molecules, and blocking the key pro-atherogenic inflammatory mechanisms can be beneficial for treatment of atherosclerosis. Therapeutic agents that specifically target some of the atherosclerosis-related inflammatory mechanisms have been evaluated in preclinical and clinical studies. The most promising anti-inflammatory compounds for treatment of atherosclerosis include non-specific anti-inflammatory drugs, phospholipase inhibitors, blockers of major inflammatory cytokines, leukotrienes, adhesion molecules, and pro-inflammatory signaling pathways, such as CCL2-CCR2 axis or p38 MAPK pathway. Ongoing studies attempt evaluating therapeutic utility of these anti-inflammatory drugs for treatment of atherosclerosis. The obtained results are important for our understanding of atherosclerosis-related inflammatory mechanisms and for designing randomized controlled studies assessing the effect of specific anti-inflammatory strategies on cardiovascular outcomes.     

Increased atherosclerosis in mice with increased vascular biglycan content

Objective

The response to retention hypothesis of atherogenesis proposes that atherosclerosis is initiated via the retention of atherogenic lipoproteins by vascular proteoglycans. Co-localization studies suggest that of all the vascular proteoglycans, biglycan is the one most closely co-localized with LDL. The goal of this study was to determine if over-expression of biglycan in hyperlipidemic mice would increase atherosclerosis development.

Methods

Transgenic mice were developed by expressing biglycan under control of the smooth muscle actin promoter, and were crossed to the LDL receptor deficient (C57BL/6 background) atherosclerotic mouse model. Biglycan transgenic and non-transgenic control mice were fed an atherogenic Western diet for 4–12 weeks.

Results

LDL receptor deficient mice overexpressing biglycan under control of the smooth muscle alpha actin promoter had increased atherosclerosis development that correlated with vascular biglycan content.

Conclusion

Increased vascular biglycan content predisposes to increased lipid retention and increased atherosclerosis development.     

HDL anti-oxidant function associates with LDL level in young adults

Objectives

The primary objective was to evaluate predictors of HDL anti-oxidant function in young adults.

Background

High-density lipoprotein (HDL) cholesterol is considered a protective factor for cardiovascular disease (CVD). However, increased levels are not always associated with decreased cardiovascular risk. A better understanding of the importance of HDL functionality and how it affects CVD risk is needed.

Methods

Fifty non-Hispanic white subjects from the Testing Responses on Youth (TROY) study were randomly selected to investigate whether differences in HDL anti-oxidant function are associated with traditional cardiovascular risk factors, including carotid intima media thickness (CIMT), arterial stiffness and other inflammatory/metabolic parameters. HDL anti-oxidant capacity was evaluated by assessing its ability to inhibit low-density lipoprotein (LDL) cholesterol oxidation by air using a DCF-based fluorescent assay and expressed as a HDL oxidant index (HOI). The associations between HOI and other variables were assessed using both linear and logistic regression.

Results

Eleven subjects (25%) had an HOI ≥ 1, indicating a pro-oxidant HDL. Age, LDL, high sensitivity C-reactive protein (hsCRP), and paraoxonase activity (PON1), but not HDL, were all associated with HOI level in univariate linear regression models. In multivariate models that mutually adjusted for these variables, LDL remained the strongest predictor of HOI (0.13 increase in HOI per 1 SD increase in LDL, 95% CI 0.04, 0.22).Atherogenic index of plasma, pulse pressure, homocysteine, glucose, insulin, CIMT and measurements of arterial stiffness were not associated with HOI in this population.

Conclusions

These results suggest LDL, hsCRP and DBP might predict HDL anti-oxidant function at an early age.