Pentraxins,Anti-pentraxin Antibodies,and Atherosclerosis

Atherosclerosis is a disease of the vascular wall, which predominantly affects large and medium-sized arteries. It represents a leading cause of morbidity and mortality in the Western world. In the last few decades, it has been clearly shown that immune system plays a relevant role in atherogenesis. The effectors of both innate and adaptive immunity, including immune cells, cell or soluble receptors, cytokines, chemokines, complement components or coagulation systems, and autoantibodies are able to modulate atherosclerosis. Among proteins belonging to innate immunity, the highly conserved pentraxin family, which encompass C-reactive protein (CRP), serum amyloid P (SAP), and the long pentraxin 3 (PTX3) seems to be directly involved in the induction and progression of atherosclerosis. By immunohistochemical staining, pentraxins were found within the atherosclerotic plaques where they could play a key role interacting with atherogenic-modified lipoproteins, favoring the formation of foam cells, and exerting a proinflammatory action. Pentraxin serum levels have been shown to be associated with clinical and subclinical atherosclerosis in general population. Antibodies against pentraxins have been demonstrated in patients with autoimmune diseases, but their role in atherogenesis is still controversial.     

脂质过氧化诱导培养的内皮细胞表达单核细胞趋化蛋白-1

在人脐静脉和牛主动脉内皮细胞培养基中加入联胺，引发其脂质过氧化损伤，观察能否诱导内皮细胞表述单核细胞起化蛋白河。用斑点杂交法检测内皮细胞暴露于联胺后其单核细胞趋化蛋白-1mRNA的表达，杂交用的探针为了r32P5’末端标记的寡核苷酸探针。同时，用酶联免疫反应检测内皮细胞暴露于联胺后．其条件培养基中的单核细胞趋化蛋白-1蛋白含量。斑点杂交显示．培养的内皮细胞可表达单核细胞趋化蛋白-1mRNA，暴露于联胺后．其单核细胞趋化蛋白-1mRNA表达水平明显升高。而且，单核细胞趋化蛋白-1mRNA表达水平与联胺的作用时间和浓度均呈正相关。酶联免疫反应显示，各组条件培养基中的单核细胞趋化蛋白-1蛋白含量亦与联胺作用的时间和浓度呈正相关。提示内皮细胞的脂质过氧化损伤可诱导其产生单核细胞起化蛋白-1增加，在动脉粥样硬化发生过程中单核细胞的聚集可能起重要作用。     

Asymptomatic hyperglycaemia is associated with increased intimal plus medial thickness of the carotid artery

Summary Atherosclerotic changes have not been demonstrated directly in asymptomatic hyperglycaemic non-diabetic subjects, although high mortality due to coronary heart disease has been reported. We measured arterial wall thickness non-invasively, in order to directly demonstrate atherosclerosis of the carotid arteries of hyperglycaemic non-diabetic subjects and to evaluate its risk factors.The thicknesses of the intimal plus medial complex (IMT) of the carotid arteries of 112 asymptomatic hyperglycaemic non-diabetic subjects (aged 22–81, 95 males and 17 females) were compared with those of 55 healthy male subjects and 211 non-insulin-dependent NIDDM male diabetic patients. The subjects were subgrouped into impaired glucose-tolerant (IGT) subjects who had a 2-h glycaemic level of more than 7.8 mmol/l, and non-IGT subjects whose 2-h glycaemic levels were within 6.7–7.7 mmol/l.Non-IGT and IGT subjects showed significantly greater IMTs than age-matched healthy males and showed no significant differences compared to age-matched NIDDM patients. Multivariate analysis demonstrated that the risk factors for IMT of non-IGT and IGT subjects were age and systolic blood pressure. According to data on the accumulation of atherogenic risks (hypertension, dyslipidaemia, and smoking), IMT increased linearly in non-IGT and IGT subjects. However, non-IGT and IGT subjects without hyperlipidaemia, hypertension, or smoking risk still had significantly greater IMT than age-matched normal males (1.019±0.063 vs 0.770±0.111 mm, p<0.05). Prevalence of ECG-indicated coronary heart disease was significantly higher in hyperglycaemic non-diabetic subjects and NIDDM with increased carotid arterial wall thickness (IMT 1.1 mm) than in those without increased thickness (IMT<1.1 mm). Asymptomatic hyperglycaemic non-diabetic subjects have increased thickness of their carotid arteries compared to age-matched male NIDDM patients. As one of several independent risk factors, mild hyperglycaemia advances atherosclerosis, which leads to coronary heart disease.Abbreviations IMT Intimal plus medial complex - NIDDM non-insulin-dependent diabetes mellitus - IGT impaired glucose tolerance - CHD coronary heart disease - T-Chol serum total cholesterol - HDL-C high-density lipoprotein cholesterol - TG serum triglycerides     

甘薯的抗家兔主动脉粥样硬化形成作用

为观察甘薯糖蛋白对家兔实验性动脉粥样硬化形成的影响并探讨其可能的发病机制。将 4 0只新西兰白兔随机分为正常组 (饲以普通饲料 )、高脂组 (饲以胆固醇饲料 )、低剂量甘薯糖蛋白 (简称低剂量 )组 [饲以胆固醇饲料 +糖蛋白 0 .0 6g/ (kg·d) ]和高剂量甘薯糖蛋白 (简称高剂量 )组 [饲以胆固醇饲料 +糖蛋白 0 .1g/ (kg·d) ]。在实验开始时和 12周时分别检测血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、超氧化物歧化酶和丙二醛含量。第 12周末处死动物 ,行主动脉病理形态学观察。结果发现 ,实验前各组血清检测指标无明显差异。实验 12周 ,高脂组、低剂量组和高剂量组血清总胆固醇、甘油三酯、低密度和高密度脂蛋白胆固醇以及丙二醛含量均高于或明显高于正常组 (正常组、高脂组、低剂量组和高剂量组的总胆固醇分别为 1.2 7± 0 .73、2 0 .2 6± 0 .13、15 .2 7± 0 .83和 11.2 8± 1.6 2mmol/L ;甘油三酯分别为 0 .85± 0 .18、1.85± 0 .35、1.71± 0 .2 8和 1.5 1± 0 .11mmol/L ;低密度脂蛋白胆固醇分别为 0 .5 0± 0 .0 7、18.99± 2 .6 5、14 .2 7± 3.0 4和 12 .13± 3.5 6mmol/L ;高密度脂蛋白胆固醇分别为 0 .5 4± 0 .11、0 .75± 0 .10、0 .81± 0 .0 6和 0 .94± 0 .0     

Increased intra-abdominal fat may lower HDL levels by increasing the fractional catabolic rate of Lp A-I in postmenopausal women

High-density lipoprotein (HDL) particles without apolipoprotein A-II (Lp A-I) may be more anti-atherogenic than HDL with apo A-II (Lp A-I/AII) and Lp A-I is reported selectively to be reduced in cases of intra-abdominal obesity. We explored the mechanisms of this reduction by studying the turnover of Lp A-I and Lp A-I/A-II in postmenopausal women well characterized for total body, regional and sub-regional adiposity by body mass index (BMI), truncal girth ratio, and abdominal magnetic resonance imaging (MRI), respectively. We tested for possible cause–effect relationships by measuring inter-correlations among these variables. Intra-abdominal fat area correlated strongly and positively with the fractional catabolic rate (FCR) of Lp A-I (r=0.98, P=0.003). Intra-abdominal fat only showed a non-significant trend toward correlation with the FCR of Lp A-I/A-II (r=0.84, P=0.07), and had no correlation with the production or transport rate (TR) of either Lp A-I or Lp A-I/A-II (r=0.48 and 0.02, respectively, P>0.1). Subjects were studied both with and without estrogen replacement, allowing exploration of a possible interaction of adiposity with estrogen effects on HDL turnover. Response of HDL turnover to estrogen did not correlate with adiposity, except for a parameter of waist to hip ratio (WHR), which predicted the increase in LP A-I TR with estrogen (r=0.84, P=0.04). We conclude that intra-abdominal fat may lower HDL levels by increasing the FCR of Lp A-I, suggesting a mechanism by which central adiposity may be proatherogenic.     

Serum Lipoprotein(a) Level and its Clinical Significance in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterised by the production of autoreactive T cells and autoantibodies that may affect every organ system. It has long been established that there is a close association between cholesterol- rich lipoproteins (such as low-density lipoprotein-cholesterol) and cardiovascular disease in patients with SLE. In this study, we evaluated total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLD-cholesterol, apolipoprotein A-1, apolipoprotein B, and cholesterol-rich serum lipoprotein(a) [Lp(a)], which is accepted to be an independent risk factor for cardiovascular disease and for atherosclerosis, in 24 patients (mean age +/- SD 31.4 +/- 9.7 years, range 16-47, 22 F) with active SLE. Twenty-six healthy age- and sex-matched (mean age +/- SD 29.7 +/- 11.3 years, range 18-49 years, 22 F) subjects were included as a control group. In patients with SLE Lp(a) levels, total cholesterol, triglycerides and VLDL-cholesterol were found to be higher and HDL-cholesterol, apolipoprotein A-1 to be lower than those of controls. In conclusion, because serum Lp(a) levels are significantly higher (P<0.01) in patients with SLE, these patients have a risk of developing cardiovascular disease and atherosclerosis. Patients with SLE should be followed up with this in mind.     

补阳还五汤对动脉粥样硬化大鼠脑缺血再灌注损伤的影响

目的：探讨补阳还五汤对早期动脉粥样硬化（动粥）大鼠脑缺血再灌注损伤的保护作用。方法：50只雄性Wistar大鼠随机分为（1）正常对照组，（2）非高脂手术组，（3）高脂假手术组，（4）高脂手术组，（5）补阳还五汤组5组，其中（3）、（4）、（5）组采用高脂饲料喂养，（5）组每天补阳还五汤灌胃，36例w后采用双侧颈动脉结扎，脑缺血45min，再灌注3d后检测血脂水平，脑组织丙二醛（MDA）、一氧化氮（NO）、一氧化氮合酶（NOS）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH－Px）的变化以及主动脉，脑组织的病理改变。结果：（1）高脂饲料喂养36w能形成早期动脉粥样硬化；（2）高脂手术组脑组织损伤较非高脂手术组严重且有显著性差异；（3）补阳还五汤能降低血脂水平，提高脑组织NOS、SOD、GSH－Px活性，并使病理改变明显减轻，结论：动脉粥样硬化可加重脑缺血再灌注损伤，补阳还五汤对粥大鼠脑缺血再灌注损伤有明显的保护作用。     

Are triglyceride-rich lipoproteins associated with aortic valve sclerosis? A preliminary report

Background: Evidence linking cardiovascular risk factors to aortic valve sclerosis (AVS) has led to the assumption that the latter is an atherosclerosis-like process. However, triglyceride (TG)-rich lipoproteins, an important risk factor for atherosclerosis, have been rarely investigated in connection with AVS. Methods: A cross-sectional study of 246 healthy individuals (mean age 59±6 years, 77% men) was conducted. Subjects underwent an echocardiographic assessment and extensive blood lipid measurements, including evaluation of TG-related indices, such as serum apolipoprotein (apo) C_II and C_III levels, apo C_III levels in VLDL+LDL particles, and apo C_III ratio (C_III level in HDL/C_III level in VLDL+LDL). Results: Twenty-three patients (9.3%) were diagnosed as having AVS. On average, these patients were 5 years older and had higher levels of serum cholesterol, LDL-C and LP(a), compared with non-AVS subjects. In addition, the AVS patients exhibited higher concentrations of serum apo C_II, serum apo C_III and apo C_III in VLDL+LDL, and a lower apo C_III ratio. Adjusting for age and gender, a 1 S.D. increment in apo C_III in VLDL+LDL was associated with odds ratio (OR) of 1.76 (95% CI: 1.17–2.65) for AVS. Further adjustment for atherosclerotic risk factors did not alter the association appreciably (OR=1.65, 95% CI: 1.06–2.58). Conclusion: TG-rich lipoproteins may be involved in the early development of AVS. Confirmation in prospective studies is required.