Morphology of the endothelium over atherosclerotic plaques in human coronary arteries

The right coronary arteries of six hearts removed from patients with atherosclerosis, who were undergoing cardiac transplantation, were perfused with 2% buffered glutaraldehyde for 20 minutes before preparation for scanning electron microscopy. Perfusion was started within five minutes of explanation. In two patients the artery was angiographically normal, in one it was irregular in outline, and three had focal segments with significant stenosis. None of the patients had concentrations of plasma lipids above 5.5 mmol/l. The endothelial surface showed widespread focal abnormalities ranging from adhesion and migration of monocytes to loss of individual endothelial cells. Larger areas of endothelial denudation with exposure of underlying collagen were also seen consistently. Loss of endothelial cells was associated with accumulation of monocytes, on and deep to the surface, as well as adhesion of platelets to the exposed subendothelial tissue. These results accord with the endothelial damage and platelet adhesion seen in hyperlipidaemic animals fed a high lipid diet.     

Morphology of the endothelium over atherosclerotic plaques in human coronary arteries.

The right coronary arteries of six hearts removed from patients with atherosclerosis, who were undergoing cardiac transplantation, were perfused with 2% buffered glutaraldehyde for 20 minutes before preparation for scanning electron microscopy. Perfusion was started within five minutes of explanation. In two patients the artery was angiographically normal, in one it was irregular in outline, and three had focal segments with significant stenosis. None of the patients had concentrations of plasma lipids above 5.5 mmol/l. The endothelial surface showed widespread focal abnormalities ranging from adhesion and migration of monocytes to loss of individual endothelial cells. Larger areas of endothelial denudation with exposure of underlying collagen were also seen consistently. Loss of endothelial cells was associated with accumulation of monocytes, on and deep to the surface, as well as adhesion of platelets to the exposed subendothelial tissue. These results accord with the endothelial damage and platelet adhesion seen in hyperlipidaemic animals fed a high lipid diet.     

Intravascular ultrasound imaging of ruptured atherosclerotic plaques in coronary arteries

Intravascular ultrasound demonstrated plaque ruptures that occurred in regions involved with large complicated atherosclerotic plaques in the coronary artery. Because intravascular ultrasound evaluates both plaque and luminal dimensions, it contributes to our understanding of the pathophysiology of coronary artery disease.     

Molecular imaging of plaques in coronary arteries with PET and SPECT

Coronary artery disease remains a major cause of mortality. Presence of atherosclerotic plaques in the coronary artery is responsible for lu-men stenosis which is often used as an indicator for determining the severity of coronary artery disease. However, the degree of coronary lumen stenosis is not often related to compromising myocardial blood flow, as most of the cardiac events that are caused by atherosclerotic plaques are the result of vulnerable plaques which are prone to rupture. Thus, identification of vulnerable plaques in coronary arteries has become increas-ingly important to assist identify patients with high cardiovascular risks. Molecular imaging with use of positron emission tomography （PET） and single photon emission computed tomography （SPECT） has fulfilled this goal by providing functional information about plaque activity which enables accurate assessment of plaque stability. This review article provides an overview of diagnostic applications of molecular imaging tech-niques in the detection of plaques in coronary arteries with PET and SPECT. New radiopharmaceuticals used in the molecular imaging of coro-nary plaques and diagnostic applications of integrated PET/CT and PET/MRI in coronary plaques are also discussed.     

血清学指标对不稳定斑块的诊断价值

目的以血管内超声-虚拟组织学（intravascularunltrasound-virtualhistology,IVUS-VH）分析为参照,观察血清学指标对不稳定斑块的预测意义。方法纳入69例冠状动脉粥样硬化性心脏病（冠心病）患者,于人院后检测各项血清学指标后,行冠状动脉造影及IVUS-vH分析斑块性质,通过受试者工作曲线（ROC）分析各项指标对不稳定斑块的诊断意义以及联合检测血清学指标对不稳定斑块的诊断符合率。结果心脏型脂肪酸结合蛋白（heart-typefattyacid-bindingprotein,HFAP）、超敏C反应蛋白（high-sensitivityC-reactiveprotein,hs-CRP）、肌钙蛋白（cardiactroponin,cTnI）受试者工作曲线下面积分别为0．833、0．692、0．647,P均〈0．05。HFAP、hs-CRP、cTnI联合检测对不稳定斑块诊断的符合率为93．75％;HFAP及hs-CRP联合检测对不稳定斑块诊断的符合率为63．16％;hs-CRP及cTnI联合检测对不稳定斑块诊断的符合率64．52％;HFAP及cTnI联合检测对不稳定斑块诊断的符合率为66．67％。结论对不稳定斑块诊断,单项检测时HFAP最优,其次为cTnI,最后为hs-CRP;HFAP、cTnI、hs-CRP三者联合检测优于任意两者联合。     

人股动脉粥样硬化斑块内尿激酶型纤溶酶原激活物受体的表达

目的选用正常乳内动脉作为对照,分析人股动脉粥样硬化斑块中尿激酶型纤溶酶原激活物受体（uPAR）在不同部位的表达差异。方法从2005年9月至2006年2月,收集我院血管外科行股动脉粥样硬化斑块剥脱术中获取的血管内膜或内-中膜标本20例,以及心脏外科行冠状动脉搭桥术中的正常乳内动脉标本16例。通过免疫组织化学染色等方法,观察uPAR在斑块中的表达情况;明确uPAR与内膜巨噬细胞、平滑肌细胞的关系;同时半定量检测斑块不同部位uPAR表达量的差异。结果uPAR在正常乳内动脉的内膜和中膜未见表达,但在粥样硬化斑块内膜uPAR的平均光密度值（A）为92±37,明显高于中膜（46±28,P〈0．05）;内膜uPAR的积分光密度值（IA）较中膜升高约7倍（P〈0．01）。内膜uPAR表达定位于巨噬细胞、泡沫细胞和平滑肌细胞处,以平滑肌细胞与uPAR分布最为一致。斑块肩部、脂质池、破裂及血栓形成部位的uPAR IA值分别为42131±31671、45747±19963和55344±23069,均明显高于相对正常部位（5072±2588,P〈0．05）,其中在斑块破裂处表达量最高。结论人股动脉粥样硬化斑块的肩部、脂质池和破裂处,uPAR表达明显升高,提示uPAR可能在斑块破裂中起着重要作用。     

Study of fibrous plaques occurring in the coronary arteries of children.

The pathology of the coronary arteries of children, in relation to atherosclerotic involvement, appeared as a pathology of the main emergence areas and branching points of the left coronary artery and particularly of the anterior descending artery. The first atherosclerotic lesions occurred as non-raised fibrous plaques in 2% of children 6--10 years old and in 4% of children and juveniles 11--15 years old. In the latter age group fatty streaks and gelatinous plaques were also seen in 6% of the subjects; in their appearance they lag behind fibrous plaques by 5--8 years. Indirect evidence was obtained that some branch pads or cushions might be converted into fibrous plaques. The transitional aspects included edema, histolysis (elastolysis, collagenolysis, ground-substance depletion and degenerative cell changes), followed by reorganization and homogeneization of the pre-existing heterogeneous microarchitecture; in a final stage the prevalent processes seemed to be the nodular proliferation of smooth muscle cells and the abundant neoformation of collagen fibers. In essence the results show that in atherosclerosis the coronary arteries are involved in a different sequence and histogenetic pattern than the aorta.     

Frequency and distribution of thin-cap fibroatheroma and ruptured plaques in human coronary arteries: a pathologic study.

OBJECTIVES: Our purpose was to quantify the frequency and distribution of suspected vulnerable lesions, defined as thin-capped fibroatheroma (TCFA) and ruptured plaque, in human coronary artery autopsy specimens. BACKGROUND: Most acute coronary events and sudden death are believed to arise from rupture of a TCFA followed by thrombosis. Although there is general agreement that clinical events are usually caused by focal lesions, there is considerable debate over the relative importance of focal versus systemic factors in the pathogenesis of atherosclerosis. METHODS: We longitudinally sectioned coronary arteries from 50 whole hearts taken from patients (mean age 73 years, 64% men) dying of cardiovascular (n = 33), noncardiovascular (n = 13), and unknown (n = 4) causes. A total of 3,639 longitudinal segments of length 3 mm were sectioned from 148 arteries, accounting for 10.9 m of total tissue length. Specimens were classified on the basis of histology and computer-aided morphometry. RESULTS: Twenty-three TCFA and 19 ruptured plaques were found (mean +/- SD: 0.46 +/- 0.95 and 0.38 +/- 0.70 per heart, respectively), and these lesions accounted for only 1.6% and 1.2%, respectively, of the total length of the coronary tree examined in patients dying of cardiovascular causes. The majority of TCFA and ruptured plaque localized in the proximal third of the major coronary arteries, and in 92% of cases these lesions clustered within 2 or fewer nonoverlapping 20-mm segments. CONCLUSIONS: The suspected precursors of rupture-mediated thrombosis occur in a limited, focal distribution in the coronary arteries.     

Quantitative morphologic studies for localizing arteriosclerotic plaques in the circumference of coronary arteries

In order to determine the distribution of arteriosclerotic plaques in the circumference of coronary arteries 150 hearts were investigated using two different methods. In 100 hearts the coronary vessels were opened longitudinally, and the sites of sclerotic lesions were mapped. The coronary arteries of another 50 hearts were filled with contrast medium, angiography was performed and the arteries were cut into 0.5-cm segments. The first 6 cm of the left anterior descending and the left circumflex arteries and the first 9 cm of the right coronary artery were studied. Segments of 1-cm length in the 100 hearts and of 0.5-cm length in the 50 hearts were examined. It was found, that arteriosclerotic lesions of the coronary arteries are most frequently located on the myocardial side of the vessel circumference. This phenomenon is most evident in the left anterior descending artery, thus possibly being caused by the most pronounced fixation of this artery on the myocardium.     

Endothelial Gi protein in human coronary arteries

Endothelium-dependent relaxations mediated by Gi protein areprominently impaired in atherosclerotic coronary arteries. However,it remains to be determined whether the expression of endothelialGi protein per se is reduced in coronary atherosclerosis. Thus,in the present study the expression of endothelial Gi proteinwas examined by immunohistochemical staining using a specificantibody against human Gi protein (-subunits of G_1–1 andG_1–2 proteins) in the proximal segment of the left anteriordescending coronary arteries (segment 6) from 40 consecutiveautopsy cases. The immunoreactive level of the Gi protein wassemi-quantitated in four grades (none, 0; slight, +; moderate,+2; high, +3) and the mean value of the ratings of all endothelialcells was used as an index of the endothelial Gi protein expressionof the artery. The immunoreactive level of the Gi protein inhuman coronary arteries was significantly reduced with ageingand extent of coronary atherosclerosis (both P<0.05), andwas lower in patients with than in those without hypertension(P<0.01) or hyperlipidaemia (P<0.05). In addition, thelevel was significantly lower in the eccentric portions thanin the concentric ones in each atherosclerotic coronary artery(P<0.0001). These alterations in the immunoreactive levelof endothelial Gi protein in human coronary arteries may explain,in part, why Gi protein-mediated, endothelium-dependent relaxationsare prominently impaired in atherosclerosis.     

Cell proliferation in human coronary arteries.

Despite the lack of direct evidence for cell multiplication, proliferation of smooth muscle cells in human atherosclerotic lesions has been assumed to play a central role in ontogeny of the plaque. We used antibodies to cell cycle-related proteins on tissue sections of human arteries and coronary atherosclerotic plaques. Specific cell types were identified by immunochemical reagents for smooth muscle, monocyte-macrophages, and other blood cells. Low rates of smooth muscle cell proliferation were observed. Macrophages were also observed with rates of proliferation comparable to that of the smooth muscle. Additional replicating cells could not be defined as belonging to specific cell types with the reagents used in this study. These findings imply that smooth muscle replication in advanced plaques is indolent and raise the possibility of a role for proliferating leukocytes.     

In vivo uptake of azithromycin in human coronary plaques

Ten patients with symptomatic coronary artery disease received oral azithromycin for 3 days and underwent directional atherectomy on the third day. Azithromycin was found in all plaque samples with a median concentration of 284 ng/ml (95% confidence interval 163 to 517 ng/ml).     

Comparison of ruptured coronary plaques in patients with unstable and stable clinical presentation

It remains uncertain why some plaque ruptures trigger acute coronary syndrome (ACS), whereas others do not. We investigated the anatomic features and tissue factor (TF) expression at the sites of plaque rupture in 42 patients presenting with ACS (n = 23) or stable angina (n = 19). Intravascular ultrasound examination was performed before directional coronary atherectomy. Specimens were stained with antibodies against TF, CD68 positive phagocytic cells, and smooth muscle cells; and intravascular ultrasound and immunohistochemistry results were compared. Baseline demographic and clinical characteristics, as well as vessel and lumen sizes at both reference and lesion sites, were comparable in the two groups. However, the remodeling index and plaque burden at lesion sites were significantly greater in the ACS than in the stable angina group. The TF-immunopositive areas were significantly greater in the ACS than in the stable angina group (0.07%; IQR [0.02–0.16%] vs. 0.02%; IQR [0.01–0.05%], P = 0.022), whereas the proportions of CD68-positive and smooth muscle cell areas were similar. There was a significant correlation between areas positive for TF and those positive for CD68 (r = 0.83, P < 0.001). In conclusion, ruptured plaques in patients with ACS show stronger TF expression, a greater plaque burden, and a higher remodeling index than do plaques in those with stable angina, suggesting that both lesion morphology and local thrombogenicity are related to clinical symptoms after plaque rupture.