Chemical composition and physical state of lipid deposits in atherosclerosis

The composition, morphology, and physical properties of lipids in atherosclerotic lesions from human aortas were studied in order to elucidate the factors for the accumulation of cholesterol and its esters in the vessel wall. Lesions were classified histologically into 3 groups: fatty streak, fibrous plaque, and advanced plaque. The relative lipid composition of the lesions was plotted on the phase diagram of the 3 major lipids: cholesterol, cholesteryl ester, and phospholipid. Early fatty streaks had compositions within the 2-phase zone with a cholesterol-phospholipid liquid crystalline phase and a cholesteryl ester oily phase. Advanced fatty streaks and fibro-fatty plaques fell within the 3-phase zone with excess free cholesterol. Advanced plaques also had an average lipid composition within the 3-phase zone, but with a larger excess of free cholesterol. From the lipid-chemical point of view there is a continuous progression from early fatty streaks through advanced fatty streaks and fibro-fatty plaques to advanced plaques. In fatty streaks the cholesteryl esters accumulate in the form of isotropic and anisotropic droplets. The latter are in the smectic liquid crystalline state with the molecules arranged in layers and have surfaces that are spherical and smooth. Fibrous and advanced plaques showed beside droplets also amorphous lipids and cholesterol monohydrate crystals. Some of the amorphous lipids were solid up to about 45 degrees C and exhibited a smectic phase at cooling, indicating cholesteryl esters as the major component. The transition temperatures of high-melting cholesteryl esters, e.g. palmitate, are depressed by low-melting ones. Most of the triglycerides are present in the cholesteryl ester droplets and abolish the cholesteric liquid crystalline phase.     

Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism

Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis—often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.     

Cholesterol crystal uptake and metabolism by P388D1 macrophages

Cholesterol monohydrate crystals are frequently detected in intermediate and advanced atherosclerotic lesions. Little is known regarding mobilization of this molecular form of cholesterol into metabolically active pools. To study a potential mechanism for mobilization of crystalline cholesterol, we examined its uptake by a mouse macrophage cell line (P388D1). Crystals were overlayered on a P388D1 cell monolayer maintained in a serum-free medium. Following incubation, the monolayer was washed, and the cells were harvested and analyzed for crystal internalization. By transmission electron microscopy, crystals were found intracellularly surrounded by a bilayer membrane. Analyses of the cellular cholesterol ester content by gas-liquid chromatography and esterification of [14C]cholesterol indicated the conversion of crystalline cholesterol to cholesterol esters. This pathway for solubilization of cholesterol crystals by macrophages could play an important role in the regression of atherosclerotic lesions.     

Intracoronary Thermography: Does It Help Us in Clinical Decision Making?

The concept of the "vulnerable" plaque has recently emerged to explain how quiescent atherosclerotic lesions evolve to cause clinical events. The morphologic and immunologic determinants specific for the vulnerable plaque have been reported: a large lipid core (>or=40% plaque volume) composed of free cholesterol crystals, cholesterol esters, and oxidized lipids impregnated with tissue factor; a thin fibrous cap depleted of smooth muscle cells and collagen; an outward (positive) remodeling; inflammatory cell infiltration of fibrous cap and adventitia (mostly monocyte-macrophages, some activated T cells, and mast cells); and increased neovascularity. Despite the large amount of information regarding the morphological characteristics of remote lesions, we lack studies with functional assessment of non-culprit lesions. Coronary thermography is a technique for functional assessment of coronary atherosclerotic plaques. Several catheter designs have been proposed. There are catheters with thermistor(s) and wires with thermal sensors at the distal tip. All designs have several advantages and disadvantages. Despite the current limitations of coronary thermography, we gained important pathophysiological and clinical information regarding the vulnerability of atheromatic plaques. It has been documented both experimentally and clinically that increased heat generation is associated with increased macrophage concentration within the plaque. The correlation between local inflammatory involvement and local heat generation has also been observed with the peripheral inflammatory markers such as C-reactive protein. Whether systemic treatment, with agents such as statins or interventional techniques, such as drug-eluting stents, will have an impact on stabilizing vulnerable plaques need to be determined in future studies. In conclusion, although there are several techniques for evaluating morphologically atheromatic plaques, thermography is a promising method for the functional assessment of vulnerable plaque and has been introduced into clinical practice, with a good predictive value for clinical events in patients with increased temperature in the atherosclerotic plaque.     

Quantification of cholesteryl esters in human and rabbit atherosclerotic plaques by magic-angle spinning (13)C-NMR

Accumulation of cholesteryl esters (CEs) is a key event in the formation of atherosclerotic plaques. More recent work suggests a role for CEs in plaque rupture leading to thrombosis, which can result in an acute event such as myocardial infarction or stroke. In this study, we present nuclear magnetic resonance (NMR) protocols for quantification of CEs in plaques in situ. Total CEs quantified by (13)C magic-angle spinning (MAS) NMR in excised plaques from human carotid arteries and rabbit aortic arteries were in good agreement with the amounts determined by subsequent standard chemical assays. The latter analysis is disadvantageous because it requires that plaque lipids be extracted from the tissue, resulting in the loss of all phase information of CEs as well as other major plaque components. With our MAS-NMR protocol, the plaque components are preserved in their native phases. Combining MAS and off-MAS NMR, we were able to quantitatively distinguish isotropic (liquid) CEs from anisotropic (liquid-crystalline) CEs in plaque tissues. In a recent study, we applied a different (13)C MAS-NMR protocol to quantify crystalline cholesterol monohydrate in plaques. Together, these 2 studies describe a new, noninvasive MAS-NMR strategy for the identification and quantification of the major lipid components in plaques in situ. This approach will be useful for investigation of the relationship between plaque rupture and specific lipids in their biologically relevant phases.     

Effect of statins on cholesterol crystallization and atherosclerotic plaque stabilization

Pleiotropic effects of statins have not been fully elucidated. Recently we demonstrated that cholesterol expands when crystallizing and may trigger plaque rupture. The present study evaluated the potential direct effects of statins in altering cholesterol crystallization as a possible mechanism for plaque stabilization independent of cholesterol lowering. Cholesterol powder was dissolved in oil with and without pravastatin, simvastatin, or atorvastatin (10 to 90 mg) and then allowed to crystallize to measure peak volume expansion (ΔVE) in graduated cylinders. Effect of ΔVE on fibrous membrane damage was also evaluated. Human coronary, carotid, and peripheral arterial plaques (65 plaques from 55 patients) were incubated with statin or saline solution using matched plaque segments to evaluate direct effects of statins on preformed crystals. Also, the effect of in vivo use of oral statins on crystal structure was examined by scanning electron microscopy and crystal content in plaques scored from 0 to +3. For all statins, ΔVE decreased significantly in a dose-dependent fashion (0.76 ± 0.1 vs 0 ml at 60 mg, p <0.001). By scanning electron microscopy crystal structure with statins had loss of pointed tip geometries, averting fibrous membrane damage. Cholesterol crystal density was markedly decreased and appeared dissolved in human plaques incubated with statins (+2.1 ± 1.1 vs +1.3 ± 1.0, p = 0.0001). Also, plaques from patients taking oral statins compared to controls had significantly more dissolving crystals (p = 0.03). In conclusion, statins decreased ΔVE by altering cholesterol crystallization and blunting sharp-tipped crystal structure and dissolving cholesterol crystals in human arteries in vivo and in vitro, providing plaque stabilization.     

胆固醇酯水解酶与动脉粥样硬化

胆固醇酯以脂滴的方式存储在胞浆内是泡沫细胞的主要特点,也是动脉粥样硬化斑块发生发展的关键因素.只有游离胆固醇才能从细胞内外流到细胞外与胆固醇接受体结合,巨噬细胞内胆固醇酯代谢的第一步就是“水解”.水解是游离胆固醇外流的限速步骤,该反应由中性胆固醇酯水解酶催化.此外,胆固醇酯水解酶还调节胆固醇逆转运,从而参与体内胆固醇的最终清除.本综述旨在分析当前各种胆固醇酯水解酶的特点,阐述其参与细胞胆固醇酯水解来调节动脉粥样硬化的作用,为进一步明确能够作为防治动脉粥样硬化形成靶点的水解酶提供线索.     

Dietary vegetable oil and wood derived plant stanol esters reduce atherosclerotic lesion size and severity in apoE*3-Leiden transgenic mice

The hypolipidemic and anti-atherosclerotic effects of vegetable oil- and wood-based dietary plant stanol esters were compared in female apoE*3-Leiden transgenic mice at relevant plasma cholesterol levels. The plant stanol esters derived from vegetable oil (sitostanol 65.7%, campestanol 30.1%) had different contents of sitostanol and campestanol than the plant stanol esters derived from wood (sitostanol 87.6%, campestanol 9.5%) or from a mixture of vegetable oil and wood (sitostanol 73.0%, campestanol 24.7%). The mice (10 per group) received for 38 weeks a control diet or diets containing 1.0% (w/w) plant stanol esters derived from either vegetable oil, wood or a mixture of both. Vegetable oil (-46%), wood (-42%) and vegetable oil/wood (-51%) plant stanol esters decreased the plasma cholesterol levels (P<0.0001) by reducing the cholesterol content in plasma very low density-, intermediate density- and to a lesser extent in low density-lipoprotein. Plant stanol ester feeding did not change plasma triglyceride levels. Dietary plant stanol esters reduced the atherosclerotic lesion area by 91+/-13% (vegetable oil), 97+/-4% (wood) and 78+/-34% (vegetable oil/wood) (P<0.0001) and the severity from regular intimal fatty streaks/mild plaques (on average type 2--3 lesions) in controls to individual intimal foam cells (相似文献   

Cholesterol crystals cause mechanical damage to biological membranes: a proposed mechanism of plaque rupture and erosion leading to arterial thrombosis

BACKGROUND: Plaque rupture and/or erosion is the leading cause of cardiovascular events; however, the process is not well understood. Although certain morphologic characteristics have been associated with ruptured plaques, these observations are of static histological images and not of the dynamics of plaque rupture. To elucidate the process of plaque rupture, we investigated the transformation of cholesterol from liquid to solid crystal to determine whether growing crystals are capable of injuring the plaque cap. HYPOTHESIS: We hypothesized that during cholesterol crystallization the spatial configuration rapidly changes, causing forceful expansion of sharp-edged crystals that can damage the plaque cap. METHODS: Two experiments were performed in vitro: first, cholesterol powder was melted in graduated cylinders and allowed to crystallize at room temperature. Volume changes from liquid to solid state were measured and timed. Second, thin biological membranes (20-40 microm) were put in the path of growing crystals to determine damage during crystallization. RESULTS: As cholesterol crystallized, the peak volume increased rapidly by up to 45% over 3 min and sharp-tipped crystals cut through and tore membranes. The amount of cholesterol and peak level of crystal growth correlated directly (r = 0.98; p < 0.01), as did the amount of cholesterol and rate of crystal growth (r = 0.99; p < 0.01). CONCLUSIONS: These observations suggest that crystallization of supersaturated cholesterol in atherosclerotic plaques can induce cap rupture and/or erosion. This novel insight may help in the development of therapeutic strategies that can alter cholesterol crystallization and prevent acute cardiovascular events.     

Changes in experimental atherosclerotic lesions of rat heart valves following long-term regression

Regression of experimental atherosclerotic lesions of rat heart valves was studied in a long-term experiment. Following a period of regression of 12 months duration, the thick superficial layers of foam cells disappeared completely. Persisting masses of cholesterol crystals did not seem to be accompanied by any cellular proliferation or fibrous reaction. Such cholesterol deposits showed peculiar transparent cystoid areas probably representing local cholesterol dissolution. The structural differences between arterial and valvular plaques can be hypothetically explained by small numbers of smooth muscle cells in the heart valves.     

Regulation of lipid droplet cholesterol efflux from macrophage foam cells

Cholesterol efflux from macrophages is the first and potentially most important step in reverse cholesterol transport, a process especially relevant to atherosclerosis and to the regression of atherosclerotic plaques. Increasingly, lipid droplet (LD) cholesteryl ester (CE) hydrolysis is being recognized as a rate-limiting step in cholesterol efflux. The traditional view on macrophage CE hydrolysis is that this pathway is entirely dependent on the action of neutral hydrolases, and numerous candidate CE hydrolases have been proposed to play a role in lipid hydrolysis in macrophages and atherogenesis. Although the exact identity of macrophage-specific CE hydrolases remains to be clarified, a common point to all of these studies is that enhancing LD-associated CE hydrolysis increases cholesterol efflux and is antiatherogenic. Understanding how cholesterol is mobilized from LDs offers new steps for modulating cholesterol efflux, and recently a role for autophagy and lysosomal acid lipase in macrophage lipolysis has emerged. Autophagy and lysosomal acid lipase thus represent novel therapeutic targets to enhance macrophage reverse cholesterol transport. This review discusses our current understanding of the relationship between macrophage LDs and atherosclerosis and presents recent insights into the mechanisms for LD CE hydrolysis in macrophage foam cells.     

Dissolving agents of human mixed cholesterol stones

Methyl tert-butyl ether which is a powerful cholesterol monohydrate solvent does not completely dissolve mixed cholesterol gallstones when directly infused into the biliary tree. In this work, we compared the effect of various solvents containing different proportions of methyl tert-butyl ether and dimethylsulfoxide in anhydrous and aqueous systems on the in vitro solubilization of human cholesterol stones. The dissolution rates of cholesterol obtained in the presence of methyl tert-butyl ether was markedly decreased when 10 p. 100 water was added. In contrast, the addition of dimethylsulfoxide (30 p. 100) to methyl tert-butyl ether-water system enhanced the stone-solvent contact, improved the cholesterol dissolution rates and left less stone debris. A subsequent dissolution with an alkaline, pH = 8.8, aqueous dimethylsulfoxide-ethylenediaminetetraacetic acid solution strongly reduced the non cholesterol residues. In vivo, nearly complete dissolution of human cholesterol stones implanted in the gallbladder of rabbits was obtained within 8 hours when methyl tert-butyl ether/dimethylsulfoxide (70/30) solvent was infused at a rate of 0.6 ml/h/kg. With methyl tert-butyl ether, only 84 p. 100 of the original stone weight was dissolved. The infusion of these solvents leads to morphological changes in the gallbladder wall with some focal ulcerations. These alterations can be almost completely recovered after two weeks. No histologic evidence of hepatic, duodenal or renal damage was found. We conclude that the mixture methyl tert-butyl ether/dimethylsulfoxide (70/30) constitutes a good solvent for mixed cholesterol stones. Compared with pure methyl tert-butyl ether, the mixed system allows for a more rapid and a more complete dissolution of gallstones.     

Experimental ultrasonic angioplasty: disruption of atherosclerotic plaques and thrombi in vitro and arterial recanalization in vivo

To investigate the use of high energy ultrasound as an alternative energy for angioplasty, an experimental ultrasonic angioplasty device was developed. The device was studied in two bioassay systems: an in vitro system for the disruption of atherosclerotic plaques and thrombi and an in vivo system for the recanalization of occluded canine femoral arteries. In vitro, sonication efficiently reduced the size of the plaques. Atheromatous plaques (n = 11) disrupted at a rate of 21 +/- 8 s/cm2; complicated plaques (n = 14) disrupted at a rate of 132 +/- 45 s/cm2 (p less than 0.001). Histologic examination revealed that the disruption of the plaques took place without concurrent damage to the media or adventitia. Ninety percent of the disrupted plaque debris had a diameter of less than 20 microns and was composed primarily of cholesterol monohydrate crystals. Solid thrombus (n = 5) weight was reduced from 1.6 +/- 0.2 to 0.4 +/- 0.1 g (p less than 0.0001) after 20 s of sonication. In vivo, sonication resulted in recanalization in all seven arteries tested in seven dogs. The obstruction was reduced from 93 +/- 11% to 18 +/- 7% (p less than 0.001). On histologic examination, the arterial wall injury index was found to be 1.56 +/- 0.42 in the test arteries compared with 1.37 +/- 0.47 in the control arteries (p = NS). The disruption of atherosclerotic plaques and thrombi, together with the efficient recanalization of the occluded arteries, demonstrates the potential of ultrasound angioplasty as a catheter-based technique for angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental atherosclerosis in hypercholesterolemic mini-pigs. Regression of cholesterol ester accumulation in aorta and coronary arteries after treatment with clofibrate, beta-pyridylcarbinol or a normo-lipidemic diet

Studies have been performed on groups of mini-pigs 21-23 months of age, which after 18 months of hypercholesterolemia (approximately 10 mmol) had developed raised atherosclerotic lesions with high levels of cholesterol esters, especially in the abdominal aorta and the coronary arteries. If the hypercholesterolemia was continued for 18 months, no significant change in the cholesterol ester content in the aorta occurred; in the coronary arteries there was a significant decrease in these older pigs. If the hypercholesterolemic pigs also were treated with beta-pyridylcarbinol the findings were very similar to the first. When hypercholesterolemic pigs were treated with clofibrate, or when the hypercholesterolemic diet was replaced with the basal food for 18 months, the plasma cholesterol level was normalized (approximately 2 mmol) within 1-2 months. The cholesterol ester content in the thoracic aorta was reduced in both groups but not that in the abdominal aorta. Clofibrate decreased the cholesterol ester level in the coronary arteries when compared to the hypercholesterolemic group; the drug also reduced the free cholesterol level when compared to the basal group. We suggest that an increased plasma cholesterol level initiated the development of the atherosclerotic lesions; their later development was only partly dependent on the plasma cholesterol level.     

Atherosclerotic plaques composed of a large core of foam cells covered with thin fibrous caps in twice-injured carotid arterial specimens obtained from high cholesterol diet-fed rabbits.

We attempted to find atherosclerotic plaques including a large lipid core and thin fibrous cap in twice-injured arterial specimens obtained from high cholesterol diet (HCD) fed rabbits. Rabbits fed a HCD were subjected to carotid artery injury using a balloon catheter. After 2 or 4 weeks of cholesterol feeding, a second mild injury was induced in the same region as the first injury. The rabbits were given a standard diet for 2 weeks after the second injury. Typical atherosclerotic plaques with a fibrous cap formed by smooth muscle cells and extracellular matrix overlying a core formed by macrophage foam cells were observed in the lesion. Gelatin proteolytic activities were found in homogenates containing either media or intima from the injured artery, and activated matrix metalloproteinase-2 (MMP2) was detected. With prolongation of the HCD feeding period (interval between injuries) from 2 weeks to 4 weeks, typical plaque was observed more frequently. Furthermore, the neointimal area and the macrophage foam cells area increased, as did gelatin-proteolytic activity. Since the typical atherosclerotic plaques observed in the present study have some histopathological and pathogenic characteristics in common with unstable atherosclerotic plaque, we expect that the typical atherosclerotic plaque found in the present study will be useful for basic studies of plaque stabilization and prevention of acute coronary syndromes.     

The usefulness of microscopic bile examination in patients with suspected microlithiasis: a prospective evaluation

Gallbladder bile collected by duodenal intubation or during surgery was examined microscopically in patients who were free of stones and in patients with proven stones. None of the 16 patients free of stones had cholesterol monohydrate crystals or calcium bilirubinate granules in bile. Among the 17 patients with proven cholelithiasis, 13 with cholesterol stones had cholesterol monohydrate crystals in their bile, but only 2 of the 4 patients with pigment stones had calcium bilirubinate granules. These data confirm that cholesterol monohydrate crystals are sensitive and specific for cholesterol stones, whereas calcium bilirubinate granules lack sensitivity for the diagnosis of pigment stones. From these results, the diagnostic usefulness of microscopic examination of bile collected from the duodenum was studied prospectively in 46 patients with symptoms suggestive of cholelithiasis but in whom stones had not been visualized at cholecystography and ultrasonography. In 15 of them, bile was found to be abnormal: cholesterol monohydrate crystals were seen in 11, cholesterol crystals + calcium bilirubinate granules in 2 and calcium bilirubinate granules in 2. To date, nine of these patients have been operated on: 6 (all with cholesterol monohydrate crystals) had small cholesterol gallstones and 3 (2 with cholesterol monohydrate crystals and 1 with calcium bilirubinate granules) had signs strongly suggestive of the recent migration of gallstones. One patient refused operation, but minute pigment stones were found to be associated with calcium bilirubinate granules at duodenal intubation. In the other 31 patients, bile contained neither cholesterol monohydrate crystals nor calcium bilirubinate granules. They were not operated on and were followed up with repeated investigations for 12 to 24 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

家兔颈总动脉不稳定斑块模型的建立

目的 建立家兔颈总动脉斑块模型。方法 选取60只雄性纯种的新西兰大白兔,随机分为3组,即球囊损伤+高脂组、高脂喂养组及普通饲料喂养组,每组20只。喂养12周后,分别给予中国斑点蝰蛇毒和组胺药物触发,诱发斑块破裂及血栓形成。结果 球囊损伤+高脂组存活17只白兔中,有38处病变狭窄程度超过50％,并且脂质核心较大、纤维帽的厚度小于65 μm,故判定以上38处病变为易损斑块。高脂喂养组中的19只白兔仅8处可判定为易损斑块;普通饲料喂养组中未见易损斑块。结论 高脂饮食饲养后,进行颈总动脉球囊拉伤制作兔易损斑块模型是切实可行的方法。     

Hypercholesterolemia causes mechanical weakening of rabbit atheroma : local collagen loss as a prerequisite of plaque rupture

Hypercholesterolemia may render atherosclerotic plaques prone to rupture. To test this hypothesis, catheters with matrix-covered balloons were implanted into the aorta of rabbits fed standard or 0. 5% cholesterol chow (n=70). In 1 month, fibrous plaques developed around the balloon. Time-dependent accumulation of cholesteryl esters and free cholesterol was detected in the plaques of the cholesterol-fed group only. The pressure needed to rupture the plaque by balloon inflation was used as an index of plaque strength. Three months after the catheter implantation, the breaking pressure was 2.1 times lower (P<0.05) in cholesterol-fed rabbits. It was accompanied by collagen loss, as measured by plaque hydroxyproline content, but not with deficiency of collagen cross-linking. Sirius red staining showed preservation of collagen originally covering the balloon and accumulation of nascent collagen in the lesions of standard chow-fed rabbits. In the cholesterol-fed group, both mature and new collagen underwent degradation predominantly in the plaque shoulders. Collagen breakdown was associated with local accumulation of foamy macrophages. Gel zymography demonstrated relative enhancement of gelatinolytic activity at 92 and 72 kDa, as well as caseinolytic activity at 57, 45, and 19 kDa in the lipid-laden plaques. Lipid accumulation in the plaque was also associated with a loss of smooth muscle cells, the cellular source of the collagen fibers. The remaining smooth muscle cells showed increased collagen synthesis, although it was insufficient to counterbalance collagen degradation and cell loss. Thus, we have obtained direct evidence that hypercholesterolemia is accompanied by enhanced local collagen degradation, which is potentially responsible for plaque weakening.     

Characterization of the relative thrombogenicity of atherosclerotic plaque components: Implications for consequences of plaque rupture

Objectives. The purpose of this study was to determine whether different components of human atherosclerotic plaques exposed to flowing blood resulted in different degrees of thrombus formation.Background. It is likely that the nature of the substrate exposed after spontaneous or angioplasty-induced plaque rupture is one factor determining whether an unstable plaque proceeds rapidly to an occlusive thrombus or persists as a nonocclusive mural thrombus. Although observational data show that plaque rupture is a potent stimulus for thrombosis, and exposed collagen is suggested to have a predominant role in thrombosis, the relative thrombogenicity of different components of human atherosclerotic plaques is not well established.Methods. We investigated thrombus formation on foam cell-rich matrix (obtained from fatty streaks), collagen-rich matrix (from sclerotic plaques), collagen-poor matrix without cholesterol crystals (from fibrolipid plaques), atheromatous core with abundant cholesterol crystals (from atheromatous plaques) and segments of normal intima derived from human aortas at necropsy. Specimens were mounted in a tubular chamber placed within an ex vivo extracorporeal perfusion system and exposed to heparinized porcine blood (mean [±SEM] activated partial thromboplastin time ratio 1.5 ± 0.04) for 5 min under high shear rate conditions (1,690 s⁻¹). Thrombus was quantitated by measurement of indium-labeled platelets and morphometric analysis. Under similar conditions, substrates were perfused with heparinized human blood (2 IU/ml) in an in vitro system, and thrombus formation was similarly evaluated.Results. Thrombus formation on atheromatous core was up to sixfold greater than that on other substrates, including collagenrich matrix (p = 0.0001) in both heterologous and homologous systems. Although the atheromatous core had a more irregular exposed surface and thrombus formation tended to increase with increasing roughness, the atheromatous core remained the most thrombogenic substrate when the substrates were normalized by the degree of irregularity as defined by the roughness index (p = 0.002).Conclusions. The atheromatous core is the most thrombogenic component of human atherosclerotic plaques. Therefore, plaques with a large atheromatous core content are at high risk of leading to acute coronary syndromes after spontaneous or mechanically induced rupture because of the increased thrombogenicity of their content.     

消瘀片消退兔腹主动脉粥样斑块作用的研究

目的 观察消瘀片对兔腹主动脉粥样斑块的消退作用。方法 采用高脂饮食８ｗ加主动脉内膜剥脱术帛成兔腹主动脉粥样硬化模型,通过血管腔内超声技术、光镜和电镜,检查口服消瘀片１６ｗ后兔腹主动脉粥样斑块的消长变化。结果 血管腔内超声检查显示,粥样硬化组管壁呈弥漫性增厚,腔内有环形或半月状粥样斑块低回声区,用消瘀片治疗后,管壁增厚不明显,仅可见散在或短弧形粥样斑块回声区,粥样斑块厚度和斑块面积与粥样硬化组相比明