Ultrasound characterization and quantification of carotid atherosclerosis lesions.

The development of ultrasonography in vascular applications has entailed research of ultrasound parameters leading to precise the diagnosis and quantification of carotid lesions in routine. The use of recent colour Doppler imaging techniques (velocity or power encoding) is recommended as they allow a better definition of the lesions and recesses. At present, features of plaque that could be related to increased incidence of stroke are: echogenicity, with a more frequent observation of anechoic or hypoechoic lesions in the case of clinical signs; texture, with frequent haemorrhage; surface contour, with a high rate of ulcerations which were accompanied by stroke; plaque motion, with a significant alteration in plaque motility in symptomatic patients; progression or regression in size, with a faster progression of anechoic and hypoechoic plaques; an increase in plaque volume is associated with a greater risk of stroke; a significant relationship between the presence of "ulcers" and embolic activity. The quantification of stenosis degree could be made using velocity criteria and/or morphological criteria. Velocity criteria could be obtained at the site of the stenosis (direct criteria) or downstream the carotid stenosis using Duplex systems. Morphological criteria could be obtained using B-mode imaging or colour Doppler but this quantification remains difficult in case of diffuse carotid stenoses or very severe stenoses.     

Diabetes influences cancer risk in patients with increased carotid atherosclerosis burden

Background and aimsAtherosclerosis and cancer share several risk factors suggesting that at least in part their pathogenesis is sustained by common mechanisms. To investigate this relation we followed a group of subjects with carotid atherosclerosis at baseline up for malignancy development.Methods and resultswe carried out an observational study exploring cancer incidence (study endpoint) in subjects with known carotid atherosclerosis at baseline (n = 766) without previous cancer or carotid vascular procedures. During the follow-up (160 ± 111 weeks) 24 cancer occurred, corresponding to an overall annual incidence rate of 0.11%. 10 diagnosis of cancer occurred in individuals with a carotid stenosis >50% (n = 90) whereas 14 in patients with a carotid stenosis <50% patients (n = 676) (p < 0.001). Respect to patients without cancer, diabetes was markedly more common in subjects with cancer diagnosis during the FU (37.3%vs75.0%, p < 0.001). After controlling for classic risk factors, carotid stenosis >50% (HR = 2.831, 95%CI = 1.034–5.714; p = 0.036) and diabetes (HR = 4.831, 95%CI = 1.506–15.501; p = 0.008) remained significantly associated with cancer diagnosis.Conclusionsto our knowledge this is the first study reporting a significant risk of cancer development in subjects with diabetes and high risk of cerebrovascular events, highlighting the need of a carefully clinical screening for cancer in diabetic patients with overt carotid atherosclerosis.     

Non-HDL cholesterol as a predictor of carotid atherosclerosis in the elderly

The aim of the present study was to evaluate sclerotic lesions of the common carotid artery by ultrasonography in 921 in-patients aged 65 years and older (77 +/- 7 years) and investigate whether lipid levels were associated with carotid atherosclerosis. In men, an increased risk for carotid atherosclerosis was associated with increased levels of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Compared to men with the lowest tertile of LDL-C levels (< 83.4 mg/dl), the adjusted odds ratio was 2.502 (95% confidence interval: 1.426-4.390) in those with the middle tertile (83.4-115.2 mg/dl), and 2.688 (1.509-4.790) in those with the highest tertile ( > 115.2 mg/dl). Like the LDL-C level, the non-HDL-C level showed a positive and linear relationship with carotid atherosclerosis. Compared to men with the lowest tertile of non-HDL-C levels ( < 101 mg/dl), the adjusted odds ratio was 2.881 (1.633-5.081) for those with the middle tertile (101-135 mg/dl), and 2.990 (1.651-5.415) for those with the highest tertile ( > 135 mg/dl). Similarly, in women, an increased risk for carotid atherosclerosis was also positively and linearly associated with LDL-C and non-HDL-C. The Non-HDL-C level is a potential predictor of risk for carotid atherosclerosis in the elderly.     

DNA shuffling as a tool for protein crystallization

The success of structural studies performed on an individual target in small scale or on many targets in the system-wide scale of structural genomics depends critically on three parameters: (i) obtaining an expression system capable of producing large quantities of the macromolecule(s) of interest, (ii) purifying this material in soluble form, and (iii) obtaining diffraction-quality crystals suitable for x-ray analysis. The attrition rate caused by these constraints is often quite high. Here, we present a strategy that addresses each of these three parameters simultaneously. Using DNA shuffling to introduce functional sequence variability into a protein of interest, we screened crude lysate supernatants for soluble variants that retain enzymatic activity. Crystallization trials performed on three WT and eight shuffled enzymes revealed two variants that crystallized readily. One of these was used to determine the high-resolution structure of the enzyme by x-ray analysis. The sequence diversity introduced through shuffling efficiently samples crystal packing space by modifying the surface properties of the enzyme. The approach demonstrated here does not require guidance as to the type of mutation necessary for improvements in expression, solubility, or crystallization. The method is scaleable and can be applied in situations where a single protein is being studied or in high-throughput structural genomics programs. Furthermore, it should be readily applied to structural studies of soluble proteins, membrane proteins, and macromolecular complexes.     

History of obesity as a risk factor for both carotid atherosclerosis and microangiopathy

As a westernized lifestyle becomes widespread in Japan, the number of individuals with obesity, as well as type 2 diabetes, is rapidly increasing. In this investigation, we studied the prevalence of obesity and its association with the development of diabetic macroangiopathy and microangiopathy. The clinical records of 634 patients in our hospital with type 2 diabetes were surveyed. The relationship between obesity and diabetic retinopathy and nephropathy and macroangiopathy (carotid artery intima-media thickness, IMT) was examined using univariate and multivariate analysis. A body mass index (BMI) > or = 25 kg/m2 was used as the diagnostic criterion for obesity. The prevalence of obesity at the time of the survey was 35% and a history of obesity was reported in 70% of the survey population. Multiple regression analysis revealed that the maximum BMI was significantly correlated with IMT thickening. The prevalence of nephropathy in previously obese patients was significantly higher than in non-obese patients. The maximum BMI was significantly associated with the development of retinopathy and nephropathy, as shown by logistic regression analysis. This suggests that a history of obesity may be an important risk factor for the development of micro- and macroangiopathy in Japanese with type 2 diabetes.     

微小RNA-130a调控人巨噬细胞三磷酸腺苷结合盒转运体A1在动脉粥样硬化的作用

目的探讨微小RNA-130a(microRNA-130a,miR-130a)靶向调控人巨噬细胞三磷酸腺苷结合盒转运体A1(ABCA1)在动脉粥样硬化的作用。方法培养人单核巨噬细胞(THP-1),分为实验组和对照组。利用lipofectamine2000转染试剂,分别将miR-130amimics或阴性对照转染到THP-1中,通过液体闪烁计数测定荷脂THP-1内胆固醇流出情况,高效液相色谱检测细胞内脂质含量;油红O染色显示细胞内脂滴情况。生物信息学软件预测miR-130a的靶基因,并利用双荧光素酶报告基因系统进行验证。通过Western blot检测靶基因ABCA1蛋白表达变化。结果实验组较对照组显著抑制THP-1内胆固醇流出[(5.24±2.36)%vs(12.58±3.92)%,P0.05]。实验组THP-1内胆固醇、胆固醇酯、游离胆固醇较对照组明显增高(P0.05),细胞内脂滴稠密且体积肥大。生物信息学分析显示,miR-130a的靶基因为ABCA1,经体外双荧光素酶报告基因系统检测,证实ABCA1是miR-130a的靶基因。实验组ABCA1蛋白表达水平较对照组明显降低(0.13±0.05 vs 0.38±0.09,P0.05)。结论 miR-130a具有调控THP-1内胆固醇流出的功能,其机制可能与靶向调控ABCA1有关。     

Lutetium texaphyrin: A new therapeutic tool for human atherosclerosis

Conclusion Photoangioplasty with ANTRIN™ represents a novel therapeutic application in human atherosclerosis. The biology of the response to photoangioplasty allows it to hold great promise as an approach to minimizing structural damage to the blood vessel at the moment of intervention. Furthermore, the direct effect of photoangioplasty on the inflammatory cellular response of the atherosclerotic vessel raises optimism for the application of this approach to the treatment and, potentially, the prevention of restenosis.     

Availability of cardio-ankle vascular index (CAVI) as a screening tool for atherosclerosis

BACKGROUND: A novel index, the cardio-ankle vascular index (CAVI), which reflects the stiffness of the aorta, femoral artery, and tibial artery, was recently developed by measuring brachial - ankle pulse wave velocity and blood pressure. METHODS AND RESULTS: In the present study 1,014 Japanese adults from the general population were screened to clarify the correlation between CAVI and other existing markers related to atherosclerosis, including carotid intima - media thickness (CIMT) and homocysteine (HCY). CAVI was strongly associated with age in both men and women. After adjustment for age and sex, CAVI was correlated with systolic and diastolic blood pressures. In addition, CAVI was significantly correlated with total cholesterol hemoglobin A(1c) and total HCY, as well as CIMT. CONCLUSION: CAVI is an appropriate screening tool for atherosclerosis, but further studies are needed to establish a convenient and effective screening system using it.     

高敏C反应蛋白与高血压病患者合并颈动脉粥样硬化的关系

目的探讨炎症标记物高敏C反应蛋白(hs-CRP)与高血压病患者中颈动脉粥样硬化发生的关系。方法对入选的202例高血压病患者进行颈动脉超声检查测量颈总动脉内膜中层厚度(IMT)、观察有无斑块形成,并进行血清hs-CRP定量检测。根据患者颈动脉粥样硬化程度、是否合并糖尿病及吸烟情况分组进行血清hs-CRP水平比较。结果(1)合并颈动脉粥样硬化的高血压病患者血清hs-CRP显著高于无颈动脉粥样硬化患者[(4.96±5.26)mg/Lvs(3.16±3.54)mg/L,P=0.006]。(2)颈动脉斑块组患者平均血清hs-CRP显著高于颈动脉正常组患者[(5.35±4.82)mg/Lvs(3.16±3.54)mg/L,P=0.002]。(3)根据吸烟情况进行分层后,1年内有吸烟行为者中颈动脉斑块硬化组患者血清hs-CRP平均值明显高于颈动脉正常组[(5.30±5.02)mg/Lvs(3.07±1.70)mg/L,P=0.024]。(4)无糖尿病的高血压病患者中,颈动脉粥样硬化组患者血清hs-CRP均值高于颈动脉正常组[(5.03±5.35)mg/Lvs(3.25±3.61)mg/L,P=0.032]。结论合并颈动脉粥样硬化尤其有颈动脉斑块的高血压病患者血清hs-CRP显著高于无颈动脉粥样硬化患者。     

Anti-chlamydophila pneumoniae antibodies as associated factor for carotid atherosclerosis in patients with AIDS

Atherosclerosis is a multifactor disease. Lately, infectious factors such as C. pneumoniae have been found to be involved. To determine whether the infection by C. pneumoniae is a risk factor for atherosclerosis in patients with AIDS. Case-control study on 43 patients with AIDS under HAART (16 cases and 27 controls). To document atherosclerosis, a carotid and transcranial Doppler ultrasound was performed. Anti-C pneumoniae antibodies were searched using a microimmunofluorescence test for IgM and IgG levels. To study the associations with risk of atherosclerosis, Odds Ratios were calculated for each IgG anti-C. pneumoniae antibody titre. A titre of 1:64 significantly increased the risk of atherosclerosis. These results suggest that hypertriglyceridemia and C. pneumoniae infection coexistence significantly increases the risk of atherosclerosis. The inverse geometric average of the antibodies titre against C. pneumoniae in individuals with atheromatous plaque fell to 64, two titres above the controls. This difference turned out to be statistically significant. Exposure to C. pneumoniae with antibodies (IgG) should be considered in any HIV diagnosed patient as a risk factor for atherosclerosis, having found that the inverse geometric averages of antibodies titre are significantly different comparing cases and controls, especially in patients with dyslipidemia, hypertriglyceridemia or in patients whose treatments could cause these conditions. In patients with concomitant hypertriglyceridemia, the association increases up to three times. It is advisable that AIDS patients take a serological test to determine exposure to C. pneumoniae, and to assess treatment options.