Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla

To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE^–/– mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 m spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.     

Detection of c, d, and e waves in the acceleration photoplethysmogram

Analyzing the acceleration photoplethysmogram (APG) is becoming increasingly important for diagnosis. However, processing an APG signal is challenging, especially if the goal is to detect its small components (c, d, and e waves). Accurate detection of c, d, and e waves is an important first step for any clinical analysis of APG signals. In this paper, a novel algorithm that can detect c, d, and e waves simultaneously in APG signals of healthy subjects that have low amplitude waves, contain fast rhythm heart beats, and suffer from non-stationary effects was developed. The performance of the proposed method was tested on 27 records collected during rest, resulting in 97.39% sensitivity and 99.82% positive predictivity.     

MRA对脑梗塞患者颅内A硬化程度的探讨

目的:通过MRA对颅内动脉硬化特征的诊断,判断患者颅内动脉硬化程度.方法:回顾性对照分析34例脑梗塞患者和30例志愿者MRA检查结果,根据血管形态、走行、血流信号改变及远端血管对脑动脉硬化程进行判断.结果:脑梗塞患者轻度硬化4例(11.76％),中度硬化12例(25.29％),重度硬化18例(52.94.％),志愿者检出动脉硬化的有18例,轻度硬化12例(66.67％),中度硬化4例(22.22％),重度硬化2例(11.11％).颅内动脉硬化与脑梗塞有很好的相关性.结论:MRA可显示颅内动脉硬化程度,作为动脉粥样硬化性脑梗死的首选影像检查方法,为脑梗死提供更多有关脑血管病变的信息.     

Inhibitory effect of Piper betel leaf extracts on copper-mediated LDL oxidation and oxLDL-induced lipid accumulation via inducing reverse cholesterol transport in macrophages

Piper betel leaf (PBL) has the biological capabilities of detoxification and can work as an anti-inflammatory agent and an anti-oxidant. In this study, we evaluated the anti-oxidative activity of the extract of Piper betel leaves (PBLs) on the basis of Cu²⁺-mediated oxidation, and its ability to prevent foam cell formation in a model for oxidised low density lipoprotein (oxLDL)-induced lipid accumulation in macrophages. Our data demonstrated that PBLs were able to inhibit LDL oxidation in vitro and are able to reduce the lipid accumulation in macrophages. We showed the underlying mechanisms to be the following: PBLs up-regulated the protein levels of the class A and class B scavenger receptors, the membrane lipid transporter ABCA1, and its upstream regulator Liver X receptor (LXR) in the macrophages exposed to oxLDL. The results suggested that PBLs activated the reverse cholesterol transport mechanism to enhance the metabolism of the oxLDL that could prevent both lipid accumulation and foam cell formation and further minimise the possible damage of vessels caused by the oxLDL.     

Polyethylene glycol-modified dendrimer-entrapped gold nanoparticles enhance CT imaging of blood pool in atherosclerotic mice

We report a new use of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for in vitro and in vivo imaging of atherosclerotic mice by computed tomography (CT). In this study, Au DENPs were synthesized using poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5.NH₂) modified by PEG monomethyl ether (G5.NH₂-mPEG₂₀) as templates. In vitro cytotoxicity and flow cytometry assays show that the formed PEGylated Au DENPs have good biocompatibility and are non-cytotoxic at the Au concentration up to 300 μM. Silver staining and transmission electron microscopy (TEM) further confirm that the Au DENPs are able to be uptaken by macrophages and are located dominantly in the lysosomes of the cells. Importantly, the formed PEGylated Au DENPs are able to be used for CT imaging of murine macrophages in vitro and macrophages in atherosclerotic mice in vivo using apolipoprotein-E-gene-deficient mice as a model. These findings suggest that the formed PEGylated Au DENPs are a promising contrast agent for CT imaging of atherosclerosis.     

Metabolism and actions of conjugated linoleic acids on atherosclerosis‐related events in vascular endothelial cells and smooth muscle cells

Conjugated linoleic acids (CLAs) are biologically highly active lipid compounds that have attracted great scientific interest due to their ability to cause either inhibition of atherosclerotic plaque development or even regression of pre‐established atherosclerotic plaques in mice, hamsters and rabbits. The underlying mechanisms of action, however, are only poorly understood. Since cell culture experiments are appropriate to gain insight into the mechanisms of action of a compound, the present review summarizes data from cell culture studies about the metabolism and the actions of CLAs on atherosclerosis‐related events in endothelial cells (ECs) and smooth muscle cells (SMCs), which are important cells contributing to atherosclerotic lesion development. Based on these studies, it can be concluded that CLAs exert several beneficial actions including inhibition of inflammatory and vasoactive mediator release from ECs and SMCs, which may help explain the anti‐atherogenic effect of CLAs observed in vivo. The observation that significant levels of CLA metabolites, which have been reported to have significant biological activities, are well detectable in ECs and SMCs indicates that the anti‐atherogenic effects observed with CLAs are presumably mediated not only by CLAs themselves but also by their metabolites.     

Soy extract has different effects compared with the isolated isoflavones on the proteome of homocysteine-stressed endothelial cells

Epidemiological studies suggest that soy consumption may provide a protection in the development and progression of atherosclerosis. It is under debate, however, whether the soy isoflavones or other compounds are the "active principle". As apoptosis is a driving force in the process of atherosclerosis, we tested whether a soy extract or a combination of the two predominant isoflavones genistein and daidzein, in concentrations as found in the extract, exert similar or different effects on apoptosis in EA.hy 926 endothelial cells after exposure to the endothelial stressor homocysteine. Plasma membrane disintegration and nuclear fragmentation served as relevant apoptosis markers. To assess whether the extract and the genistein/daidzein mixture differently affect cellular target proteins changed in amount by homocysteine treatment, proteome analysis was performed by two-dimensional gel-electrophoresis and peptide mass fingerprinting of regulated protein spots. Homocysteine induced apoptosis in the cells, and both extract and genistein/daidzein inhibited apoptosis to a comparable extent. Whereas the extract prevented for 10 proteins the changes in expression levels as caused by homocysteine, the genistein/daidzein mixture reversed the homocysteine effects on the proteome for 13 proteins. The cytoskeletal protein matrin 3 and a U5 snRNP-specific 40-kDa protein were the only protein entities where both extract and genistein/daidzein reversed the homocysteine-induced changes in a common way. In conclusion, our studies provide evidence that an isoflavone containing soy extract and isolated isoflavones, despite similar effects on inhibition of homocysteine-induced apoptosis in endothelial cells, affect a quite different spectrum of cellular target proteins.     

The Carotid Artery Plaque Size and Echogenicity are Related to Different Cardiovascular Risk Factors in the Elderly

Carotid plaques can be characterised by ultrasound by size and echogenicity. Both size and echogenicity are predictors of cardiovascular events. The aim of this study was to examine whether traditional risk factors and markers of inflammation and oxidation were associated with plaque size and echogenicity. Computerised analysis of carotid plaque size and echogenicity (grey scale median, GSM) were performed by ultrasound in a population-based health survey in 1,016 subjects aged 70 years (PIVUS study). Information on cardiovascular risk factors was collected, together with markers of inflammation and oxidation. Increased Framingham risk score, systolic blood pressure, higher BMI and decreased HDL, lower glutathione levels were related to echolucent plaques. Previous or present smoking was common with significantly more pack-years related to the echorich plaques. Plaque size was associated with increased Framingham risk score, systolic blood pressure, blood glucose levels, smoking, ApoB/A1 ratio, OxLDL, TNF alpha, HOMA insulin resistance, leucocyte count, decreased BCD-LDL and low levels of l-selectin. Low HDL, increased BMI and decreased glutathione levels were associated with the echolucency of carotid plaques, implying metabolic factors to play a role for plaque composition. Markers of inflammation were related to plaque size alone, implying inflammation to be predominantly associated with the amount of atherosclerosis. These results suggest that plaque size and echogenicity are influenced by different risk factors.