The carotid atherosclerotic plaque and microembolisation during carotid stenting

Microembolisation is an important issue in carotid artery stenting. During different phases in the stenting process, numerous emboli are dislodged from the atherosclerotic plaque. Embolisation can be measured as microembolic signals detected by transcranial Doppler (TCD) monitoring during the procedure or as new ischemic areas determined by magnetic resonance imaging. This article gives an overview of the principles of emboli detection methods, their clinical relevance, and risk factors associated with microembolisation. In addition, protection devices are discussed in relation to embolisation. Although they potentially protect the brain, particularly filter devices increase the amount of TCD-detected cerebral microemboli. Special attention is paid to the carotid artery plaque, which is subject to ongoing research that may yield important implications for clinical practice in the near future. Evidence is accumulating that unstable, vulnerable plaques are associated with increased microembolisation during carotid interventions. This knowledge of the vulnerable plaque can be translated to the clinical setting by plaque imaging. A first approach has been made by duplex imaging of carotid plaque morphology. More advanced methods such as molecular magnetic resonance imaging and optical coherence tomography could aid in optimal treatment selection based on plaque characteristics thus reducing microembolisation and associated cerebral adverse events.     

Cyclosporin A affects axons and macrophages during Wallerian degeneration

A traumatic injury of a peripheral nerve leads to Wallerian degeneration. It includes the recruitment of macrophages and the phagocytosis of myelin and the remnants of axons. We have previously studied the recruitment of macrophages and now wished to determine if the immunosuppressant cyclosporin A (CsA) affects the number of macrophages at the site of nerve injury. The primary target of CsA is T-cells, but it may also have an effect on mononuclear phagocytes which exert a key role during Wallerian degeneration. Rats were divided into two groups: CsA-treated animals and control animals. Following transection of the sciatic nerve in the treatment group, the animals received 5 mg/kg CsA subcutaneously. The groups were further subdivided into a freely regenerating nerve group and a sutured nerve group. The number of macrophages and MHC class II positive cells were counted 3 days, 7 days, 2 weeks, 4 weeks, and 8 weeks posttransection; also CD4, CD8, IL-2 receptor positive cells, B cells, and the axonal sprouting were studied. In the CsA-treated group, there were more macrophages in the distal areas under 8 weeks than in the controls (p < 0.05); thus, the clearance of macrophages is delayed in the CsA-treated rats compared to the control rats. In the proximal area, the difference in macrophage number did not gain statistical significance. Additionally, CsA retarded axonal degeneration. CsA affects number of macrophages during Wallerian degeneration, while retarding axonal degeneration and subsequent reinnervation. Its mechanism of action appears to involve either direct or indirect via T-cells-mediated responses.     

Excess parathyroid hormone adversely affects lipid metabolism in chronic renal failure

Hyperlipidemia is common in chronic renal failure (CRF), but the underlying mechanisms are not clearly defined. Certain data points toward a potential role for the state of secondary hyperparathyroidism of CRF in its pathogenesis. We examined the effects of parathyroid hormone (PTH) on lipid metabolism utilizing intravenous fat tolerance test (IVFTT) and post-heparin lipolytic activity in five normal dogs, in six animals with CRF and secondary hyperparathyroidism (NPX) and in six normocalcemic-thyroparathyroidectomized dogs (NPX-PTX) with comparable degree and duration of CRF. NPX dogs had fasting hypertriglyceridemia (82 + 6.0 mg/dl vs. 49 +/- 2.7 mg/dl in normal dogs, P less than 0.01), abnormal IVFTT, and reduced post-heparin plasma LPL activity (151 +/- 10 vs. 275 +/- 15 mumol fatty acids/ml/min in normal dogs, P less than 0.01). The NPX-PTX dogs had normal fasting levels of serum triglycerides (42 +/- 0.6 mg/dl), normal IVFTT, and normal post-heparin plasma LPL (317 +/- 19 mumol fatty acids/ml/min) despite CRF. Post-heparin HL activity in plasma was not different between NPX and NPX-TPX dogs. The results show that excess blood levels of PTH and not other consequences of CRF are mainly responsible for the abnormalities in lipid metabolism. The data are consistent with the notion that excess PTH reduces post-heparin LPL activity in plasma, which in turn results in impaired lipid removal from the circulation and consequently hyperlipidemia.     

ApoE-/-小鼠肾动脉粥样硬化斑块破裂的肾损害

目的 探讨ApoE^-/-小鼠肾动脉粥样硬化斑块破裂对下游肾脏的损伤机制。 方法 采用ApoE^-/-小鼠建立粥样硬化性肾动脉狭窄(ARAS)动物模型。选择肾动脉狭窄程度 <50％的ApoE^-/-小鼠，按斑块分为破裂组和未破裂组；选择同条件喂养的C57BL/6J 野生型小鼠为对照组。常规检测Scr及尿 N-乙酰-β-氨基葡萄糖苷酶(NAG)活性；Western印迹检测细胞核中核转录因子κBp65（NF-κBp65）、细胞间黏附分子1（ICAM-1）及P-选择素（P-sel）表达； RT-PCR检测白细胞介素6 （IL-6）mRNA表达；免疫组化染色检测巨噬细胞浸润情况。 结果破裂组Scr和尿NAG活性明显升高（均P < 0.01）；肾组织出现病理改变，肾间质中巨噬细胞浸润增加（P < 0.05）；细胞核中NF-κBp65表达增加（P < 0.05）；ICAM-1、P-sel、IL-6 mRNA表达增加（P < 0.05）。未破裂组上述指标与对照组比较，差异无统计学意义（P > 0.05）；肾脏未见明显病理改变。 结论 肾动脉粥样硬化斑块破裂可引起肾脏病理改变和肾功能受损；在粥样硬化性肾动脉狭窄的肾损害机制中，炎性反应是重要因素之一。     

幽门螺杆菌热休克蛋白60诱导的抗原调节性T细胞及其对小鼠动脉粥样硬化的影响

目的 观察幽门螺杆菌热休克蛋白60(HP-HSP60)诱导的抗原特异性T细胞接种对ApoE~(-/-)小鼠动脉粥样硬化斑块的影响.方法 制备小鼠骨髓单核细胞,体外诱导HP-HSP60特异性调节性T细胞分化,并接种CD4~+CD25~+T_(reg)细胞后,观察其对小鼠动脉粥样斑块形成的影响.结果 阿司匹林处理的树突状细胞CDS0(43.0%)和CD86(41.1%)表达减少,形态学表现为未成熟树突状细胞,但其能诱导更多的特异性CD4~+CD25~+T_(reg)细胞(13.0±1.94)%,实验组粥样斑块面积(2.37±0.96)mm~2显著小于对照组(P<0.05).结论 未成熟树突状细胞可诱导出HSP60抗原特异性调节性CD4~+CD25~+T_(reg)细胞,后者在体内能明显抑制动脉粥样斑块的形成.     

Chlamydia pneumoniae infection induces an unstable atherosclerotic plaque phenotype in LDL-receptor, ApoE double knockout mice.

OBJECTIVES: To study whether Chlamydia pneumoniae (Cpn) infection affects atherosclerotic plaque morphology in atherogenic (LDLr/ApoE(-/-)) mice. METHODS: In mice sacrificed 20 or 40 weeks after Cpn infection aortic arch sections were analysed for lesion and fibrous cap area and the presence of matrix metalloproteinases (MMP)-2 and -9. RESULTS: All infected mice seroconverted, demonstrated Cpn DNA in their aortas on PCR and developed atherosclerotic plaques. Infection was not associated with changes in lesion area or type, but was associated with reduced the fibrous cap area and increased MMP-2 and -9 immunoreactivity. CONCLUSION: These findings suggest that Cpn infection may predispose to plaque instability.     

Severe acute hypophosphatemia during renal replacement therapy adversely affects outcome of critically ill patients with acute kidney injury

Purpose

Hypophosphatemia during renal replacement therapy (RRT) is common in critically ill patients with acute kidney injury (AKI). The clinical consequences of RRT-induced phosphate depletion are not well defined in this patient population, and there is no evidence that intravenous sodium phosphate supplementation (PS) prevents the clinical sequelae of acute hypophosphatemia. The purpose of this retrospective analysis of the Acute Renal Support Registry of the University of Munich was to examine the association between severe hypophosphatemia and severity of and recovery from AKI.

Methods

289 ICU patients with AKI on intermittent hemodialysis (IHD) were included in the study. One hundred and forty-nine patients received PS during IHD. Outcomes were short-term (at discharge) and long-term (at 1 year) recovery of renal function and mortality.

Results

The two patient groups did not differ in demographics, clinical features, renal characteristics, and frequency of hypophosphatemia at initiation of IHD. Without PS, the frequency of hypophosphatemia increased from 20 to 35%. Severe hypophosphatemia was found in 50% of these patients. By comparison, PS was not associated with an increased frequency of hypophosphatemia. Compared with patients with acute phosphate depletion, patients receiving PS developed less oliguria during IHD, had shorter duration of AKI, higher incidence of complete renal recovery at discharge, and a lower risk of de novo chronic kidney disease. Hypophosphatemia was associated with higher all-cause in-hospital mortality and higher risk of long-term mortality.

Conclusions

This multicenter study indicates for the first time that hypophosphatemia during IHD adversely affects short- and long-term outcome of critically-ill patients with AKI. The clinical consequences of the acute hypophosphatemic syndrome may be prevented by PS.     

Diabetes affects sorbitol and myo-inositol levels of neuroectodermal tissue during embryogenesis in rat

ATP, ADP, phosphocreatine (PCr), creatine (Cr), glucose, malate, sorbitol, and myo-inositol (MI) were measured by quantitative histochemical techniques in pure neuroectodermal tissue of rat embryos of gestation days 11 and 12 that were dissected from normal and streptozocin-induced diabetic mothers. Neither gestational age nor maternal diabetes affected the tissue's energy potential (ATP-to-ADP and PCr-to-Cr ratios). Diabetes resulted in a fourfold rise in the embryonic glucose and a 25% increase in neuroectodermal malate content. Maternal hyperglycemia caused a rise in fetal sorbitol at days 11 and 12 of gestation. The MI content of the neuroectoderm was not affected by the maternal diabetic state in perfusion embryos (day 11); however, the near doubling of MI that occurs from day 11 to day 12 during normal development was prevented. Thus, embryos isolated from diabetic mothers on gestation day 12 had 30% less MI than embryos isolated from normal mothers. From these data we conclude that a rise in tissue sorbitol is not always accompanied by a fall in tissue MI. These results and recent information in the literature implicate involvement of decreased MI concentrations in the process leading to malformation of the nervous system in diabetic embryopathy.     

Angiogenesis in atherosclerotic plaque obtained from carotid endarterectomy: association between symptomatology and plaque morphology

Carotid plaque with hemorrhage leads to cerebral embolism and ischemic stroke. Plaque angiogenesis and angiogenetic factors such as vascular endothelial growth factor (VEGF) are critical in the progression of atherosclerotic carotid plaque and intraplaque hemorrhage. The correlation between plaque angiogenesis and presence of clinical symptoms was studied in 41 specimens obtained during carotid endarterectomy from 20 symptomatic and 21 asymptomatic patients treated for carotid artery stenosis. Histological findings using hematoxylin-eosin and immunohistochemical staining against von Willebrand factor and VEGF were examined. Intraplaque hemorrhage, calcification, necrosis, and invasion of foam cells were frequently observed in the carotid plaques from symptomatic patients compared with asymptomatic patients. Higher microvessel density was found in the carotid plaques with necrosis and invasion of foam cells compared with plaques without necrosis and/or foam cell invasion, and higher expression of VEGF was found from symptomatic patients compared with asymptomatic patents. These results suggest that plaque angiogenesis and higher level of VEGF expression may enhance the progression of ischemic symptoms in patients with carotid artery stenosis. Invasive macrophages in the plaque of symptomatic patients increase levels of VEGF and might enhance plaque angiogenesis and atherosclerosis progression.     

Running wheel accessibility affects the regional electroencephalogram during sleep in mice

Regional aspects of sleep homeostasis were investigated in mice provided with a running wheel for several weeks. Electroencephalogram (EEG) spectra of the primary motor (frontal) and somatosensory cortex (parietal) were recorded for three consecutive days. On a single day (day 2) the wheel was locked to prevent running. Wheel running correlated negatively with the frontal-parietal ratio of slow-wave activity (EEG power between 0.75 and 4.0 Hz) in the first 2 h after sleep onset (r = -0.60; P < 0.01). On day 2 frontal EEG power (2.25-8.0 Hz) in non-rapid eye movement sleep exceeded the level of the previous day, indicating that the diverse behaviors replacing wheel-running elicited more pronounced regional EEG differences. The frontal-parietal power ratio of the lower frequency bin (0.75-1.0 Hz) in the first 2 h of sleep after dark onset correlated positively with the duration of the preceding waking (r = 0.64; P < 0.001), whereas the power ratio in the remaining frequencies of the delta band (1.25-4.0 Hz) was unrelated to waking. The data suggest that in mice EEG power in the lower frequency, corresponding to the slow oscillations described in cats and humans, is related to local sleep homeostasis.     

Rate of atherosclerotic plaque formation predicts cardiovascular events in ESRD

Carotid intima media thickness (IMT) is a strong, independent predictor of cardiovascular events in both the general population and among those with end-stage renal disease (ESRD), but it is unknown whether changes in IMT or other ultrasound-measured indicators of atherosclerosis over time provide additional prognostic information. The progression of atherosclerosis with carotid ultrasound was followed in a cohort of 135 ESRD patients, 103 of whom had a repeat ultrasound after 15 mo of follow-up. The number of plaques and the proportion of patients with severe atherosclerosis increased substantially during the follow-up period, but IMT, common carotid artery diameter, common carotid artery wall-to-lumen ratio, and cross-sectional area, did not change. The rate of formation of new plaques was a strong, independent predictor of incident cardiovascular events, even after adjusting for baseline plaque burden and other potential confounders. New plaque formation over time was independently predicted by background plaque burden and serum C-reactive protein (P = 0.004 and P = 0.02, respectively). Changes in IMT and the other ultrasound-measured indicators of atherosclerosis progression did not predict cardiovascular outcomes. Therefore, monitoring IMT over time is unlikely to provide additional prognostic information compared with a single measurement, but longitudinal ultrasound monitoring of plaque formation may be useful for cardiovascular risk stratification in the ESRD population.     

MRI诊断颈动脉粥样硬化斑块成分的Meta分析

目的通过Meta分析方法评价MRI判断颈动脉粥样硬化斑块成分的价值。方法系统检索2017年10月前发表的与MRI颈动脉粥样硬化斑块成分分析相关,并以病理学诊断为金标准的中、英文研究文献。文献纳入与排除标准参考Cochrane协作网所推荐的内容确定。采用RevMan 5.3软件对纳入文献的研究资料进行统计学分析,并以诊断性试验准确性质量评价(QUADAS)标准进行质量评价。结果最终纳入文献7篇,共包含813个颈动脉粥样硬化斑块。以病理结果为金标准,MRI识别颈动脉粥样硬化斑块脂质核心的95%CI为(0.80,1.27),比值比(OR)为1.01,Z值为0.06,P值为0.95;识别钙化成分的95%CI为(0.64,1.11),OR为0.85,Z值为1.19,P值为0.23。结论 MRI用以识别颈动脉粥样硬化斑块中的脂质核心及钙化成分具有较高临床价值。     

Gray-scale median of the atherosclerotic plaque can predict success of lumen re-entry during subintimal femoral-popliteal angioplasty

OBJECTIVE: This study assessed whether the duplex ultrasound (DUS)-derived gray-scale median (GSM) of the most six distal portion of the occluded femoral-popliteal arterial segment can predict success of lumen re-entry for subintimal angioplasty. METHODS: During the last 3 years, 108 patients (62% men) with a mean age of 73 +/- 10 years underwent 116 primary attempted DUS-guided subintimal angioplasties of the femoral-popliteal segment. Preprocedural B-mode DUS images of the plaque at the most distal occlusion segment were digitalized and normalized using Photoshop (Adobe, San Jose, Calif) software and standard criteria (gray level, 0 to 5 for lumen blood and 185 to 190 for the adventitia on a linear scale of 0 to 255). Overall GSM of the plaque segment about 2 cm long, immediately before the planned re-entry point to the true arterial lumen, was used for retrospective correlation with procedure success and other clinical indicators. RESULTS: Mean plaque GSM for all cases was 22.5 +/- 12.6 (range, 3 to 60). The overall success rate of subintimal angioplasty procedures was 85%. Mean plaque GSM for 99 successful cases (18.4 +/- 7.8) was significantly lower than for 17 cases (46.4 +/- 8.1) where we failed (P < .0001). We failed in 90% of 19 cases with GSM >35, in 71% of 24 cases with GSM >20, and in 50% of 34 cases with GSM >25. There was no statistically significant difference (P = .45) between plaque GSM in 64 patients with diabetes (23.3 +/- 13.5) compared with 52 nondiabetic patients (21.5 +/- 11.4). Similarly, plaque GSM was not statistically different (P = .9) in 52 patients with renal insufficiency (22.7 +/- 13.2) compared with 64 patients with normal creatinine levels (22.4 +/- 12.2). At the 6-month follow-up, no statistically significant difference was found between mean GSM (17.8 +/- 7.8) in 47 stenosis-free cases compared with mean GSM (18 +/- 6.8) in 22 cases where severe restenosis (>70%) or reocclusion was identified by DUS scan (P = .4). CONCLUSIONS: Plaque echogenicity represented by DUS-derived GSM can be used to predict the success of primary subintimal femoral-popliteal angioplasties.     

Protein quality affects bone status during moderate protein restriction in growing mice

Adequate protein intake during development is critical to ensure optimal bone gain and to attain a higher peak bone mass later on. We hypothesized that the quality of the dietary protein is of prime importance for bone physiology during moderate protein restriction. The target population was growing Balb/C mice. We compared two protein restricted diets (6% of total energy as protein), one based on soy (LP-SOY) and one based on casein (LP-CAS). For comparison, a normal protein soy-based control group (NP-SOY) and a low protein group receiving an anabolic daily parathyroid hormone (PTH) 1-34 injection (LP-SOY + PTH) were included in the protocol. After 8 weeks, LP-SOY mice had reduced body weights related to a lower lean mass whereas LP-CAS mice were not different from the NP-SOY group. LP-SOY mice were characterized by lower femoral cortical thickness, bone volume, trabecular number and thickness and increased medullar adiposity when compared to both the LP-CAS and NP-SOY groups. However, the dietary intervention had no effect on the vertebral parameters. The negative effect of the LP-SOY diet was correlated to an impaired bone formation as shown by the reduced P1NP serum level as well as the reduced osteoid surfaces and bone formation rate in the femur. PTH injection in LP-SOY mice had no effect on total weight or lean mass, but improved all bone parameters at both femoral and vertebral sites, suggesting that amino acid deficiency was not the primary reason for degraded bone status in mice consuming soy protein. In conclusion, our study showed that under the same protein restriction (6% of energy), a soy diet leads to impaired bone health whereas a casein diet has little effect when compared to a normal protein control.     

Relationship between ADAMTS4 and carotid atherosclerotic plaque vulnerability in humans

Background

Rupture of atherosclerotic plaques and the resulting thrombosis are vital causes of clinical ischemic events. Recent studies have shown that ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) is a pathogenic factor of plaque vulnerability in mice. However, the relationship between ADAMTS4 and carotid atherosclerotic vulnerable plaques in humans remains unclear.

超声评价颈动脉粥样硬化斑块稳定性的研究进展

动脉粥样硬化和不稳定斑块的存在是心脑血管事件发生最重要的危险因素之一,颈动脉不稳定斑块的脱落或破裂也是导致脑卒中的主要病因。本文对超声评价颈动脉粥样硬化斑块的稳定性及其与相关影像学技术的比较进行综述。