Lipid droplets in atherosclerotic fatty streaks of human aorta

Preparations of lipid droplets and droplet-free tissue residue (cytoplasm + membranes + nuclei) were obtained by homogenization and centrifugal separation from intimal fatty streak lesions of aortic atherosclerosis of 21 adults who had died suddenly. Neutral lipids and phospholipids were analyzed by quantitative thin-layer chromatography and cholesteryl ester fatty acids by gas-liquid chromatography. Optical properties of droplets were evaluated by differential counting and sizing procedures with the polarizing microscope. The droplets occurred in mixtures of two forms distinguished by their optical properties, anisotropic (i.e. liquid crystals) and isotropic (true liquids). Both forms had average diameters of about 1.8 mu, with a range of 0.5-5mu. The proportions of the two forms varied with temperature as individual droplets changed their form; anisotropic forms averaged 83.7% at degrees C and 37.8% at 37 degrees C, with isotropic forms being 16.3 and 62.2% respectively. The proportions of anisotropic forms at 22 degrees C decreased with age. These forms were not separated for chemical analysis. The droplets contained about half the lipid in the lesions. The composition of the lipids of the droplet mixture was remarkably uniform and strikingly different from that of the droplet-free residue, respectively: cholesteryl esters 94.9% vs. 38.7%, free cholesterol 1.7% vs. 18.6%, total phospholipids 1.0% vs. 38.6%, and triglycerides 2.4% vs. 4.0%. The proportions of individual phospholipids, with the exception of lysolecithin, were also different between the preparations. In the droplets only the proportions of lecithin correlated positively with the proportion of anisotropic forms (at 22 degrees C). Droplet cholesteryl esters were particularly rich in oleic acid and when compared to residue esters had more palmitoleic (+0.7%), oleic (+12.3%), and eicosatrienoic (+2.4%) and less palmitic (-2.2%), linoleic (-12.4%), and arachidonic (-1.6%) acids. The proportions of most individual fatty acids of droplets and residue correlated positively. The lipids of the residue closely resemble those reported for the normal intima.The observations that these droplets are prominent in the morphology of the fatty streak lesions, and that their high content of oleate-rich cholesteryl esters is similar to that reported for analysis of the whole lesions, suggest that the droplets may be involved in the pathogenesis of the fatty streak lesions of artherosclerosis in man.     

Age-associated changes in human carotid atherosclerotic plaques

Little is known about changes in carotid plaque morphology during aging and the possible impact on cardiovascular events. Only few studies addressed so far age-related modifications within atherosclerotic lesions. Therefore, in this work we endeavored to summarize the current knowledge about changing of plaque composition in elderly. The data from hitherto existing studies confirm that atherosclerotic plaques undergo distinct alternations with advanced age. However, the results are often ambiguous and the changes do not seem to be as disastrous as expected. Interestingly, none of the studies could definitely evidence increased plaque vulnerability with advanced age. Nevertheless, based on the previous work showing decrease in elastin fibers, fibroatheroma, SMCs, overall cellularity and increase in the area of lipid core, hemorrhage, and calcification, the plaque morphology appears to transform toward unstable plaques. Otherwise, even if inflammatory cells often accumulate in plaques of younger patients, their amount is reduced in the older age and so far no clear association has been observed between thin fibrous cap and aging. Thus, the accurate contribution of age-related changes in plaque morphology to cardiovascular events has yet to be elucidated.

• KEY MESSAGES

• Composition of carotid atherosclerotic lesions changes during aging. These alternations are however, just moderate and depend upon additional variables, such as life style, accompanying disease, genetics, and other factors that have yet to be determined.

• Based on the current data, the age-associated plaque morphology seems to transform toward vulnerable plaques. However, the changes do not seem to be as disastrous as expected.

     

健康体检者颈动脉粥样硬化斑块形成相关危险因素的研究

目的分析颈动脉粥样硬化斑块形成相关危险因素,以采取早期预防措施。方法对1256例体检者经超声检查颈动脉,测量颈动脉内-中膜厚度,分析体质量指数、高血压、血脂异常、糖尿病等与颈动脉硬化之间的关系。结果 1256例体检者,共检出颈动脉粥样硬化442例,其中高体质量指数组18例,血脂异常组41例,高血压组38例,高血压合并血脂异常组48例,糖尿病组23例,吸烟组29例,对照组8例。各危险组与对照组差异有统计学意义(P0.05),且高血压合并血脂异常、与单纯性高血压、血脂异常比较,差异有统计学意义(P0.05)。结论血脂异常是颈动脉硬化的主要危险因素之一,血脂异常及高血压两者同时存在可加重动脉粥样硬化。     

Intimal preatherosclerotic thickening of the coronary arteries in human fetuses of smoker mothers

Summary.  Background : Many studies have described the development of preatherosclerotic coronary artery lesions in infancy. The observations reported in the literature regarding the fetal origin of coronary artery lesions are rare and controversial. Objectives : To identify the features of preatherosclerotic coronary artery lesions in late fetal stillborns and the possible atherogenic role of maternal cigarette smoking. Methods : We examined 22 stillborns (13 males and nine females), all of whom had died sine causa after the 32nd week of gestation. All underwent autopsy. Twelve of the mothers smoked over five cigarettes per day before and during the pregnancy. The four major epicardial coronary arteries were isolated along their whole length, embedded in paraffin and serially cut for histologic examination and immunohistochemical studies, particularly searching for the proliferating cell nuclear antigen and c-Fos expression. Alterations of chromosome 7 were also investigated by the fluorescence in situ hybridization technique. Results : In over 50% of the fetuses, almost all from smoker mothers, multifocal structural alterations of coronary walls were evident. The smooth muscle cells (SMCs) presented loss of polarity, forming columns perpendicular to the axis of the media and infiltrating the subendothelial connective tissue. Increased amounts of mucoid ground substance were also observed in the subendothelial connective tissue. In all the cases with coronary alterations, study of the biological markers showed intense c-Fos positivity of the SMCs. Conclusions : Preatherosclerotic intimal alterations of the coronary arteries are already detectable in the prenatal period and are significantly associated with maternal cigarette smoking.     

动脉粥样硬化经高强度聚焦超声作用后血管的结构和功能变化

目的 观察高强度聚焦超声（HIFU）在体辐照兔粥样硬化腹主动脉后血管的结构和功能变化，探讨HIFU对病理性血管的影响。方法建立粥样硬化兔动物模型，经HIFU辐照后，通过光镜、透射电镜、彩色多普勒血流显像（CDFI）和数字减影血管造影（DSA）测定血管组织形态学和血流动力学变化。结果 经HIFU辐照后，兔动物模型粥样硬化腹主动脉出现一定程度损伤，但无血管栓塞和破裂，实验组和对照组血管损伤程度差异无统计学意义；CDFI系列血流参数均下降（P〈0．05）；DSA显示动脉血流阻滞，充盈延迟，无血管栓塞和破裂。辐照后5d及10d观察损伤血管呈逐渐恢复趋势，动脉血流参数呈恢复趋势，对照组恢复更好。结论 HIFU辐照兔粥样硬化腹主动脉将导致可逆性损伤和血流动力学改变。     

Expression of lipoprotein lipase mRNA and secretion in macrophages isolated from human atherosclerotic aorta.

The expression of lipoprotein lipase (LPL) mRNA and the LPL activity were studied in macrophages (CD14 positive) from human atherosclerotic tissue. Macrophages were isolated after collagenase digestion by immunomagnetic isolation. About 90% of the cells were foam cells with oil red O positive lipid droplets. To analyze the mRNA expression, PCR with specific primers for LPL was used. Arterial macrophages were analyzed directly after isolation and the data showed low expression of LPL mRNA when compared with monocyte-derived macrophages. To induce the expression of LPL mRNA in macrophages, PMA was used. When incubating arterial macrophages with PMA for 24 h we could not detect any increase in LPL mRNA levels. Similarly, the cells secreted very small amounts of LPL even after PMA stimulation. In conclusion, these studies show a very low expression of LPL mRNA in the CD14-positive macrophage-derived foam cells isolated from human atherosclerotic tissue. These data suggest that the CD14-positive cells are a subpopulation of foam cells that express low levels of lipoprotein lipase, and the lipid content could be a major factor for downregulation of LPL. However, the cells were isolated from advanced atherosclerotic lesions, and these findings may not reflect the situation in early fatty streaks.     

Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta.

Osteopontin is a phosphorylated, sialic acid-rich, noncollagenous bone matrix protein containing the Arg-Gly-Asp-Ser amino acid sequence responsible for cell adhesion. The protein strongly binds to hydroxyapatite and play an important role in calcification. Expression of osteopontin mRNA was analyzed in human aortic atherosclerotic lesion by Northern blot hybridization, as well as by in situ hybridization. The expression of osteopontin mRNA was detected in 24 out of 25 samples of aorta obtained from 17 autopsy cases, but not in one normal aortic sample. The magnitude of expression was proportional to the stage of atherosclerosis. In situ hybridization revealed that the cells expressing osteopontin mRNA were detected in the wall surrounding atheroma and closely associated with calcification. They were morphologically identified as foam cells and immunohistologically positive with HHF35, appearing to be derived from smooth muscle cells. These findings have suggested that smooth muscle cell-derived foam cells express osteopontin mRNA and play an important role in calcification of the atherosclerotic lesions.     

硬化大脑中动脉及豆纹支管壁弹性结构改变及意义

本文用光镜、电镜观察了正常和硬化大脑中动脉及其豆纹支管壁弹性结构的形态。结果显示，硬化大脑中动脉内弹力膜断裂，且以外层断裂明显，波纹状外观消失；而豆纹支内弹力膜结构完整，波纹状外观清晰可见。平滑肌萎缩、变性，胶原纤维增多。提示硬化大脑中动脉破裂出血是内弹力膜破坏，平滑肌萎缩，管壁脆性增加所致；而豆纹动脉是根部存在＂中膜缺损＂，此外受血流冲击引起破裂的可能性大。     

Adiponectin levels and atherosclerotic risk factors in pediatric chronic peritoneal dialysis patients.

BACKGROUND: Atherosclerotic vascular diseases are the major cause of mortality in patients with end-stage renal disease (ESRD) treated with chronic peritoneal dialysis (CPD), even in children. Adiponectin (ADPN) is a recently discovered adipocyte-derived plasma protein having anti-atherogenic properties. ADPN levels are elevated in ESRD but it has been reported that ESRD patients with low plasma ADPN levels have a high risk of cardiovascular death. OBJECTIVE: To clarify the atherosclerotic risk and especially the significance of ADPN levels in pediatric patients on CPD. DESIGN: Cross-sectional studyin the pediatric peritoneal dialysis unit of a university hospital. PATIENTS: 18 children, aged 12.6 +/- 5.6 years, being treated with CPD and 20 healthy age- and sex-matched control subjects were enrolled in this study. METHODS: Serum ADPN levels and other risk factors, including blood pressure, blood glucose, serum lipid/lipoprotein fractions, apolipoprotein B, C-reactive protein (CRP), lipoprotein(a), and homocysteine levels, were studied in CPD patients and compared to the controls. RESULTS: Serum ADPN levels were three times higher in the CPD group compared to the control subjects, as was previously reported. Apolipoprotein B and CRP levels were also high in the CPD group. No significant difference was found in other atherosclerotic parameters, including lipoprotein(a) and homocysteine levels. Interestingly, we found a negative correlation between log ADPN and creatinine levels among the CPD patients (r = -0.54, p < 0.05). There was no correlation between log ADPN and duration of CPD. Creatinine and low-density lipoprotein levels could account for 54% of the total variation in ADPN levels. CONCLUSION: Among pediatric CPD patients, serum levels of the anti-atherogenic protein, ADPN, were inversely associated with creatinine. ADPN level might be a novel marker to predict prognosis in pediatric CPD patients.     

粥样硬化兔腹主动脉缩窄近端和远端内膜巨噬细胞与树突细胞的变化

目的观察粥样硬化兔腹主动脉缩窄近端和远端内膜巨噬细胞与树突细胞的变化。方法将同批兔随机分为高脂饲料组15只和普通饲料组10只,喂养28周后对高脂组10只、普通组5只手术结扎腹主动脉造成管腔缩窄,余普通组5只和高脂组5只给予假手术,术后分为高脂手术组,普通手术组,普通假手术组和高脂假手术组,继续喂养4周后对各组兔腹主动脉多处测量血压,取血管行免疫组化染色,观察随血压的变化,高脂手术组兔腹主动脉缩窄近端、远端内膜巨噬细胞和树突细胞的变化。结果(1)高脂饲料组(包括高脂手术组和高脂对照组)血三酰甘油和胆固醇均高于普通饲料组;(2)高脂手术组缩窄近端腹主动脉血压高于高脂假手术组近端,而缩窄远端血压则低于高脂假手术组;(3)普通对照组血管内膜薄而光滑;高脂组血管内膜有大量泡沫细胞堆积;高脂手术组腹主动脉缩窄近端内膜比高脂假手术组近端内膜厚,缩窄远端内膜比高脂假手术组远端内膜薄;(4)高脂手术组缩窄近端内膜巨噬细胞和树突细胞的数量均多于高脂假手术组近端,缩窄远端少于高脂假手术组远端。结论粥样硬化兔腹主动脉缩窄近端血压高,内膜厚,巨噬细胞和树突细胞数量多,推测斑块不稳定性增高;缩窄远端血压低,内膜薄,巨噬细胞和树突细胞数量少,推测斑块不稳定性降低。     

Non-traditional risk factors for atherosclerotic disease: A review for emergency physicians

Introduction

Acute coronary syndrome (ACS) is a life-threatening disease frequently managed in the Emergency Department (ED). Risk factors such as age, hypertension, diabetes mellitus, obesity, and smoking are classically associated with atherosclerosis and ACS.

空腹血糖相关危险因素十年变化趋势

目的:了解空腹血糖相关危险因素随时间变化趋势,以便针对性的制定有效的糖尿痛预防策略.方法:利用同一地区相隔十年两次横断面调查所收集数据,按空腹血糖程度不同进行分组:空腹血糖正常组(空腹血糖<6.1 mmol/L)、空腹血糖升高组(空腹血糖≥6.1 mmol/L).比较两次调查及每次调查各组间差异.比较分析两次调查空腹血糖相关危险因素差异及变化趋势.结果:(1)1983-1984年血糖升高占被调查人数1.06%(75/7066),1993-1994年血糖升高占被调查人数5.55%(353/6362).(2)多元线形回归分析:1983-1984年甘油三酯(TG)、总胆固醇(TG)、年龄进入方程.1993-1994年:除上述因素外平均收缩压(SBP)、平均舒张压(DBP)、体重指数(BMI)、身高腰围比(Whtr)、腰臀围比(WHR)、高密度脂蛋白(HDL)也进入方程.(3)logistic多因素非条件回归分析显示1983-1984年有年龄、TC、TG进入方程;1993-1994年除上述因素外还有糖尿家族病史、职业、血压、Whtr进入方程.结论:空腹血糖危险因素随时间的迁移有明显的增多细化趋势.增龄、血脂紊乱为空腹血糖升高持续稳定的危险因素;高血压、Whtr不是20世纪80年代空腹血糖升高的主要危险因素.     

Effect of niceritrol on lipid metabolism of aorta in atherosclerotic rats

Atherosclerotic lesions were formed in the aorta of rats given a high cholesterol diet containing propylthiouracil (PTU) and vitamin D2 (atherogenic diet) for 8 weeks. The effects of niceritrol (pentaerythritol tetranicotinate), which lower the plasma lipid level, on lipid metabolism in the arterial wall of the atherosclerotic rats were studied. Niceritrol significantly decreased the plasma cholesterol level of atherosclerotic rats, which was 823 mg/100 ml, or about ten times that of control rats. On treatment with niceritrol, the cholesterol level was reduced most in the very low density lipoprotein (VLDL) fraction (d less than 1.006). Heparin-releasable lipoprotein lipase activity in epididymal adipose tissue, lipoprotein lipase activity in post-heparin plasma, and VLDL-triolein hydrolyzing activity in adipose tissue stromal vessels were all higher in niceritrol-treated atherosclerotic rats. Of the enzymes in the arterial wall concerned with cholesterol ester metabolism, acid cholesterol esterase activity was decreased in atherosclerotic rats, while niceritrol treatment increased this activity. The ratio of acyl-CoA cholesterol acyltransferase activity (ACAT) to neutral cholesterol esterase activity was higher in atherosclerotic rats than in control rats, but was lower in niceritrol-treated rats than in atherosclerotic rats. From these results, it is concluded that niceritrol modifies enzyme activities in such a way as to reduce the cholesterol ester content of the arterial wall and lower plasma VLDL and LDL cholesterol levels.     

巨噬细胞MRI检测兔早期腹主动脉粥样硬化斑块

目的 观察巨噬细胞MRI在检测兔早期动脉粥样硬化斑块中的应用价值。方法 将10只健康新西兰兔随机均分为模型组及对照组,对模型组通过球囊拉伤联合高脂饲料建立腹主动脉粥样硬化模型,对照组不予任何干预。对两组动物行MR扫描,检测静脉注射葡聚糖四氧化三铁纳米颗粒（DCIONP）对比剂前及注射后45 min、24 h、48 h、72 h、96 h和120 h 血管壁信号强度（SI）及信号强度变化值（ΔSI）。之后处死动物,病理观察动脉粥样硬化斑块。结果 模型组斑块注射DCIONP后45 min SI升至最高,48 h开始低于注射前水平,96 h降至最低;对照组管壁于注射DCIONP后45 min均匀强化,24 h后SI基本恢复至注射前水平,其后SI无明显变化。两组间各时间点ΔSI差异均有统计学意义（P均<0.05）。病理结果表明血管壁信号衰减区与斑块内铁蓝染区及巨噬细胞分布相符。结论 巨噬细胞MRI可检测兔早期动脉粥样硬化斑块,可能具有潜在临床应用价值。