Detection of dissection and remodeling of atherosclerotic lesions in rabbits after balloon angioplasty by magnetic-resonance imaging

OBJECTIVE: To assess the usefulness of magnetic-resonance imaging (MRI) for monitoring acute changes after angioplasty of preexisting lesions in rabbits with basal lesions similar to those observed in humans. METHODS: A combination of Fogarty balloon injury (1 week after initiation of diet) and a mildly hypercholesterolemic diet (0.2% cholesterol and 5% peanut oil) was used to promote the rapid formation of atherosclerotic lesions in 16 New Zealand white rabbits. After 5 months of the diet, angioplasty was performed on these lesions with a Grüntzig catheter in both iliac arteries and the abdominal aorta. MRI was used to monitor the initial formation of lesions after 3 and 5 months of the diet, and 2 days, 2 weeks, and 1 and 2 months after angioplasty. RESULTS: The combination of early Fogarty injury and mildly hypercholesterolemic diet induced fibroproliferative lesions similar to type Vb atherosclerotic lesions seen in humans. Angioplasty induced deep dissections at the shoulders of lesions in the majority of animals. These dissections often extended into the media. The cellular, proliferative response after angioplasty was localized and limited to sites of dissection. A significant increase in area of arterial wall was observed after angioplasty at sites of dissection without any loss of lumen. In contrast, proximal and distal to the sites of injury, there was no change in wall area but a transient reduction in lumen area. CONCLUSIONS: Comparison of MRI results with histology confirmed that changes in the wall and lumen, including small linear dissections in the lesions and arterial remodeling, are detectable by MRI.     

光学相干断层成像下青年女性急性冠状动脉综合征患者的斑块特征分析

目的:通过使用光学相干断层成像(OCT)分析青年女性急性冠状动脉综合征(ACS)患者冠状动脉斑块特征。方法:纳入北京安贞医院2014年12月至2018年1月,因ACS入院行OCT且年龄≤40岁的29例青年女性患者,通过冠状动脉造影及OCT对患者冠状动脉的狭窄程度及斑块特征进行分析,探讨青年女性患者的冠状动脉斑块特点。结果:29例青年女性患者的造影中,25例(86. 2%)累及LAD,其中18例(86. 2%)为单支病变。对29例青年女性患者的29处靶血管进行OCT检查,结果显示:26例(89. 7%)病变为TCFA病变,15例(51. 7%)病变观察到巨噬细胞聚集,6例(20. 7%)观察到微通道,9例(31. 0%)病变处合并斑块侵蚀,1例(3. 4%)合并斑块破裂。结论:青年女性ACS患者多同时合并多种危险因素,且其斑块易损性高,其发生冠状动脉事件的病理学基础可能为斑块侵蚀而非斑块破裂。     

Characterization of apoptosis induced by protein kinase C inhibitors and its modulation by the caspase pathway in acute promyelocytic leukaemia

Acute promyelocytic leukaemia (APL;M3) is a unique form of acute myelogenous leukaemia characterized by t(15;17) translocation. The induction of apoptosis via inhibiting protein kinase C (PKC) has been recently viewed as a promising tool for the eradication of several malignant disorders. In the present study, we investigated the effect of two different protein kinase C inhibitors, Gö6976 and safingol, on the induction of apoptosis in the APL cell line NB4 and its all trans retinoic acid (ATRA)‐resistant variant NB4.306. The effect of the PKC inhibitors on leukaemic cells obtained from three APL patients was also studied. We also evaluated the possible involvement of the caspases in apoptosis induced by PKC inhibitors. Significant time‐ and concentration‐dependent apoptotic changes were demonstrated using Gö6976 and safingol. In addition, our results demonstrated that the caspases were involved in the apoptosis induced by the PKC inhibitors. In conclusion, our study illustrates that the PKC inhibitors Gö6976 and safingol induce apoptosis in APL and hence could be potential therapeutic agents for the treatment of this disease.     

Vascular 131I-low-density lipoprotein imaging in patients with hypertension and early atherosclerotic lesions in the carotid artery.

BACKGROUND: The reinjection of autologous 131I-labelled low-density lipoprotein (LDL) followed by vascular scintigraphy has been used to investigate lipid-containing plaques, but no information is available on the early stages of plaques in hypertensives. Vascular scintigraphy after re-injection of autologous 131I-labelled LDL was used to investigate early atherosclerotic lesions visualized by sonography in the carotid arteries of patients with hypertension. PATIENTS AND METHODS: 10 male patients (4 smokers; mean age 56 +/- 8 years;) with early carotid atherosclerosis (mono- or bilateral; intima-media-thickness ranging from 1.5 to 3.5 mm) as shown by sonography were studied. All these normolipemic patients suffered from primary hypertension and were treated with diuretics. As controls 6 healthy male subjects (3 smokers; mean age 54 +/- 9 years;), with normal blood pressure and lipid pattern were recruited. RESULTS: Hot spots appeared in the areas with early atherosclerosis in 7 patients, while none were seen in controls. Positive kinetic curves were observed in 4 patients. No significant differences emerged in the target/non-target ratios. CONCLUSIONS: Vascular lipoprotein uptake in hypertensive patients is apparently late and rather limited; the uptake pattern may depend on plaque composition.     

Effect of dietary copper supplementation on cell composition and apoptosis in atherosclerotic lesions of cholesterol-fed rabbits

We have previously shown that dietary copper supplementation modulates the formation of atherosclerotic lesions in the cholesterol-fed rabbit. In the present study, we have investigated the effects of copper supplementation on the cellular composition and characteristics of atherosclerotic lesions in cholesterol-fed NZW rabbits. Rabbits received a 1% cholesterol diet with or without 0.02% copper acetate (containing 12 and 0.3 mg copper per 100 g diet, respectively) for 12 weeks. The tunica intima was significantly smaller in the animals receiving copper supplements (0.016+/-0.005 vs. 0.068+/-0.019 mm(2), P<0.05) and this was accompanied by a significant increase in aortic copper content (4.0+/-0.8 vs. 1.8+/-0.2 microg/g tissue, P<0.05). The percentage area staining for smooth muscle cells (HHF-35 positive) was significantly lower in the intima of animals receiving copper supplements (7.13+/-1.02 vs. 9.72+/-0.82%, P<0.05). However, there were no significant differences in area staining for macrophages (RAM-11 positive) between groups (22.6+/-7.9 vs. 23.3+/-4.9%). There were also significantly fewer apoptotic cells (0.96+/-0.33 vs. 2.54+/-0.56%, P<0.005) in the aortic intima from animals supplemented with copper, but no difference in the number of proliferating cells. However, there was a reduction in intimal collagen staining (Sirius red positivity) in the animals receiving a copper supplement. Taken together, these data show that dietary copper can significantly affect the composition and progression of atherosclerotic lesions.     

Different prevalence of asymptomatic atherosclerotic lesions in males and females.

The detection of atherosclerotic lesions in asymptomatic healthy subjects is possible using ultrasound. Populations can be investigated in order to detect differences in early and asymptomatic atherosclerosis due to gender and risk factors. This study investigated 2605 male (21-69 years) and 1601 female (20-70 years) employees and civil servants of the city of Düsseldorf, Germany. The ultrasound investigations were performed with an ATL device, type Ultramark 4 plus, and a 7.5-MHz linear transducer on the carotid and proximal femoral arteries. An atherosclerotic lesion was defined as visibly different from the intima by its echogenicity and by being larger than 1 mm. A thickening of the intima media complex was not considered to be atherosclerosis. The prevalence of atherosclerotic lesions in male subjects was higher than those in female subjects regardless of age. In male subjects it was 5.3% (30-39 years), 19.8% (40-49 years), 36.7% (50-59 years) and 47.7% (60-70 years). The female subjects had a prevalence of 2.1%, 8.4%, 17.5% and 37.7% in the corresponding age groups. Risk factors such as smoking, hypertension and hypercholesterolemia were higher in men than in women. The increase of atherosclerotic lesions from one decade to another was highest in women between 50 and 59 years and 60 and 70 years. This large increase could not be explained by a similar increase in risk factors. It was therefore concluded that male subjects had a higher prevalence of atherosclerosis at earlier ages than females, but female subjects showed a postmenopausal rise in prevalence.     

Multidetector-row computed tomography and magnetic resonance imaging of atherosclerotic lesions in human ex vivo coronary arteries

In the present study, we tested the ability of multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) to identify and retrospectively characterize atherosclerotic lesions in human ex vivo coronary arteries. Thirteen ex vivo hearts were studied with MDCT and MRI. MDCT-images were obtained with an isotropic voxel size of 0.6mm(3). MR images were obtained with an in-plane resolution of 195 microm and 3mm slice thickness. All images were matched with histopathology sections. For both modalities, the sensitivity for the detection of any atherosclerotic lesion was evaluated, and a retrospective analysis of plaque morphology according to criteria defined by the American Heart Association (AHA) was performed. At histopathology, 28 atherosclerotic lesions were found. 21 and 23 of these lesions were identified by MDCT and MRI, respectively. Both modalities detected a small number of false-positive lesions. After retrospective matching with histopathology, MDCT as well as MRI were able to differentiate typical morpholocigal features for fatty, fibrous or calcified plaque components. Using the information presented in this study, in vivo coronary artery wall imaging using MDCT as well as MRI could be facilitated and supported for future investigations on this subject.     

Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability

Leukotrienes (LT) are a group of proinflammatory lipid mediators that are implicated in the pathogenesis and progression of atherosclerosis. Here we report that mRNA levels for the three key proteins in LTB4 biosynthesis, namely 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTA4 hydrolase (LTA4H), are significantly increased in human atherosclerotic plaque (n = 72) as compared with healthy controls (n = 6). Neither LTC4 synthase nor any of the LT receptors exhibits significantly increased mRNA levels. Immunohistochemical staining revealed abundant expression of 5-LO, FLAP, and LTA4H protein, colocalizing in macrophages of intimal lesions. Human lesion tissue converts arachidonic acid into significant amounts of LTB4, and a selective, tight-binding LTA4H inhibitor can block this activity. Furthermore, expression of 5-LO and LTA4H, but not FLAP, is increased in patients with recent or ongoing symptoms of plaque instability, and medication with warfarin correlates with increased levels of FLAP mRNA. In contrast to human plaques, levels of 5-LO mRNA are not significantly increased in plaque tissues from two atherosclerosis-prone mouse strains, and mouse plaques exhibit segregated cellular expression of LTA4H and 5-LO as well as strong increases of CysLT1 and CysLT2 mRNA. These discrepancies indicate that phenotypic changes in the synthesis and action of LT in specific mouse models of atherosclerosis should be cautiously translated into human pathology. The abundant expression of LTA4H and correlation with plaque instability identify LTA4H as a potential target for pharmacological intervention in treatment of human atherosclerosis.     

Characterization of acute and subacute radiofrequency ablation lesions with nonenhanced magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) has the potential to visualize radiofrequency (RF) ablations, which have become the preferred strategy for treatment of many arrhythmias. However, MRI patterns after RF ablation have not been well investigated. OBJECTIVE: The purpose of this study was to define the characteristic appearance and the effect of time and energy on noncontrast-enhanced MRI of RF ablation. METHODS: Using a power-controlled, cooled-tip ablation system, RF ablation lesions (5-50 W for 45 seconds) were created on the right ventricular epicardium in 10 mongrel dogs. T1- and T2-weighted MR images were obtained during 12-hour follow-up and compared with gross anatomy and histopathology. RESULTS: Lesions were successfully visualized with T2- and T1-weighted images 30 minutes to 12 hours after RF ablation. T2 images were more consistent and displayed a characteristic elliptical, high-signal core (contrast-to-noise-ratio [CNR] = 18.9 +/- 8.4) with a surrounding 0.5-mm low-intensity rim that on histopathology corresponded to the central tissue necrosis and the transition zone, respectively. T1 images showed a less remarked increase in signal intensity (CNR = 9.6 +/- 7.4) without a surrounding rim. Lesion size and appearance were well defined and unchanged during the 12-hour follow-up (analysis of variance). CNR was independent of applied RF energy and allowed accurate assessment of RF ablation at all time points (r = 0.87 and r = 0.83 for T2 and T1 images, respectively). Transmural lesions, interlesional gaps, and intralesional pathology could be reliably predicted in >90%. CONCLUSION: Noncontrast-enhanced MRI allows accurate assessment of RF ablation and its intralesional pathology during 12-hour follow-up. This finding confirms a possible role of MRI in guiding and evaluating RF application during electrophysiologic ablation procedures.     

Advances in transesophageal echocardiography for the evaluation of atherosclerotic lesions in thoracic aorta--the effects of hypertension, hypercholesterolemia, and aging on atherosclerotic lesions.

We assessed atherosclerotic lesions in the thoracic aorta in 166 consecutive patients (aged 56 +/- 13 years) by transesophageal echocardiography, and investigated the influences of hypertension, hypercholesterolemia and age on the prevalence of such lesions. Satisfactory images were obtained of all the thoracic aorta, except for a small part of the ascending aorta, by use of a biplane transesophageal probe. We defined atherosclerotic lesions as increased echogenicity of the intima (intimal thickening), raised plaque, calcification, ulceration, or aneurysms. Lesions were observed in 97 patients (58%). The incidence of lesions in patients with hypertension (81%) or hypercholesterolemia (80%) was significantly greater than in those without both conditions (37%, p less than 0.005). The incidence of lesions was significantly increased among patients over 60 years old compared with that in patients under 60 (76% vs 42%, p less than 0.005). Patients without either hypertension or hypercholesterolemia showed a marked increase in the incidence of lesions with age (16% at less than 60 yrs vs. 67% at greater than 60 yrs), and no significant influence of these conditions on the incidence of lesions was found in patients over 60. We conclude that hypertension and hypercholesterolemia might be important risk factors for the development of atherosclerotic lesions in the thoracic aorta in relatively younger patients. Age appears to become a more important determinant of such lesions in Japanese patients over 60 years old irrespective of blood pressure and serum cholesterol levels.     

A sensitive and specific assay for 5-methoxytryptophol in plasma.

5-Methoxytryptophol (ML) is found in the pineal gland and is known to have biological activity especially as an antigonadotrophic agent, but methods have been lacking for its measurement in the circulation. A gas chromatography-mass spectrometry assay using a trimethylsilyl derivative has been developed for the routine measurement of ML in plasma. The assay is of great specificity and has a sensitivity of 20 pmol/l. Studies on the levels of pineal indoles in the circulation, however, have been hampered by the possibility that extraneous compounds are being cross-measured. Thus the specificity of the routine assay has been further validated by comparing it with an alternative assay system where all the major parameters were changed, i.e. derivatizing reagent, internal standard and mass number. Results that were obtained using both assay systems were closely comparable.