CETP and LCAT Gene Polymorphisms Are Associated with High‐Density Lipoprotein Subclasses and Acute Coronary Syndrome

We evaluated whether CETP and LCAT gene polymorphisms are statistically associated with the high‐density lipoprotein (HDL) size distribution, the cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5′ exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a subgroup of 100 healthy individuals was recruited; the HDL subclasses were separated via ultracentrifugation and polyacrylamide gradient gel electrophoresis under native conditions. Under a dominant model, the G allele of the rs708272 polymorphism was associated with an increased risk of ACS (odds ratios [OR] = 1.45, corrected p‐value [pC_Dom] = 0.036). The linkage disequilibrium analysis showed that one of the eight possible combinations was associated with the risk of developing ACS (OR = 1.52, pC = 0.02), which suggests that it may contribute to coronary atherosclerosis. The rs708272 G allele carriers had a lower concentration of cholesterol associated with the HDL2a and HDL3a subclasses when compared with subjects carrying the A allele. Carriers of LCAT rs2292318 A allele showed a lower concentration of high‐density lipoprotein‐cholesterol (HDL‐C) in comparison to the GG genotype; the cholesterol associated with the each one of the five HDL subclasses was significantly lower in rs2292318 A than in GG subjects. In summary, this study demonstrates that the rs708272 polymorphism is associated with a heightened risk of developing ACS. In addition, we report the association of the rs708272 and rs2292318 polymorphisms with HDL‐C levels and HDL subclasses.     

Hibiscus sabdariffa leaf polyphenolic extract inhibits LDL oxidation and foam cell formation involving up-regulation of LXRα/ABCA1 pathway

The oxidative modification of low-density lipoprotein (LDL) is involved in the pathogenesis of atherosclerotic lesions through the formation of macrophage-derived foam cells. In the present study, we aimed to investigate the anti-atherosclerotic effect of Hibiscus sabdariffa leaf polyphenolic extract (HLP), which is rich in flavonoid. The inhibitory effect of HLP on oxidation and lipid peroxidation of LDL was defined in vitro. HLP showed potential in reducing foam cell formation and intracellular lipid accumulation in oxidised-LDL (ox-LDL)-induced macrophage J774A.1 cells under non-cytotoxic concentrations. Molecular data showed these influences of HLP might be mediated via liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) pathway, as demonstrated by the transfection of LXRα siRNA. Our data implied that HLP up-regulated the LXRα/ABCA1 pathway, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that HLP potentially could be developed as an anti-atherosclerotic agent.     

Vascular calcification: Inducers and inhibitors

Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.     

Design,optimization and numerical simulation of a MicroFlow sensor in the realistic model of human aorta

Among all arterial diseases, aneurysm and atherosclerosis are of great importance. In these diseases the cross-section area of the artery and therefore the blood flow velocity changes. Therefore, it is a good idea to use a micro flow sensor for measuring the blood flow velocity to diagnosing these diseases. In this study, design, geometric optimization and numerical simulation of a hotfilm microsensor in the realistic model of human's aorta are investigated. A normal aorta geometry is extracted from CT Angiography images, and after applying oscillating boundary conditions on the inlet and outlet arteries, blood flow parameters are investigated by computational fluid dynamics (CFD) simulation. After designing the microsensor, the effects of its location in different aorta regions on the blood flow characteristics are numerically investigated. The results show that in the presence of microsensor, streamlines patterns almost remain unchanged while the maximum blood flow velocity in the aorta cross section where the microsensor is located, increases up to 10%. It is also found that the secondary flow weakens when the microsensor enters the artery causing a reduction in velocity measurement error. Furthermore, because of the presence of a catheter, the pressure drop increases up to 768 Pa. Results show that less than 30% of the arterial cross-sectional area where the microsensor is located, senses an increase in temperature.     

VASCULAR CELLS RESPOND TO ENDOTHELIAL CELL FLOW- AND PRESSURE-RELEASED SOLUBLE PROTEINS

Arterial homeostasis is dictated by hemodynamics and intercellular communications. Therefore, the present study exposed vascular cells to mechanical forces and conditioned medium to determine the impact of intracellular communication on cell responses. Endothelial cells exposed to flow and flow-conditioned medium demonstrated the most significant up regulation of COX-2 (p < 0.01), ecNOS (p < 0.01), and PDGF-B (p < 0.05) mRNA. When exposed to pressure and control medium, endothelial cells expressed COX-2 (p < 0.01), ecNOS (p < 0.01), and PDGF-B (p < 0.01) mRNA to a lesser extent than cells exposed to flow and control medium. In addition, cell growth studies in the presence of flow- and pressure-conditioned medium revealed decreased (p < 0.05) endothelial cell growth and increased (p < 0.05) smooth muscle cell growth. Ultimately, understanding the effects of chemical mediators released by vascular cells under physiological and pathological conditions will aid in elucidating the development and progression of atherosclerosis.     

Hydrokinetic approach to large-scale cardiovascular blood flow

We present a computational method for commodity hardware-based clinical cardiovascular diagnosis based on accurate simulation of cardiovascular blood flow. Our approach leverages the flexibility of the Lattice Boltzmann method to implementation on high-performance, commodity hardware, such as Graphical Processing Units. We developed the procedure for the analysis of real-life cardiovascular blood flow case studies, namely, anatomic data acquisition, geometry and mesh generation, flow simulation and data analysis and visualization. We demonstrate the usefulness of our computational tool through a set of large-scale simulations of the flow patterns associated with the arterial tree of a patient which involves two hundred million computational cells. The simulations show evidence of a very rich and heterogeneous endothelial shear stress pattern (ESS), a quantity of recognized key relevance to the localization and progression of major cardiovascular diseases, such as atherosclerosis, and set the stage for future studies involving pulsatile flows.     

叶黄素对早期动脉粥样硬化的保护作用及其机制

叶黄素是类胡萝卜素之一,因其具有独特的生物活性而备受关注。它含有羟基和多个共轭不饱和双键结构,具有抗氧化作用,能够抑制LDL过氧化损伤和抑制血管内皮细胞黏附分子的过度表达,对早期动脉粥样硬化可能具有保护作用。重点介绍了叶黄素对早期动脉粥样硬化的保护作用及其机制的研究进展。     

白藜芦醇对兔动脉粥样硬化基质金属蛋白酶表达的影响

目的探讨白藜芦醇对实验性动脉粥样硬化兔基质金属蛋白酶(MMP)表达的影响。方法选择新西兰纯种雄性大白兔50只随机分为三组,正常对照组10只,模型组20只,白藜芦醇组20只。采用液氮冻伤术建立动脉硬化模型,造模2个月后采用液氮冻伤术激发动脉硬化斑块破裂,模后2个月及激发试验后48h后分别对三组动物测定MMP-1、9的浓度。结果模型组造模后2个月MMP-1、9的浓度分别为(50.74±5.49)ng/ml和(337.69±8.98)ng/ml,同期白藜芦醇组MMP-1、9的浓度分别为(41.33±9.58)ng/ml和(309.83±10.59)ng/ml(P<0.01),激发试验48h后模型组MMP-1、9的浓度分别为(100.35±6.58)ng/ml和(869.56±12.37)ng/ml,同期白藜芦醇组MMP-1、9的浓度分别为(61.68±11.69)ng/ml和(411.24±15.74)ng/ml(P<0.01)。结论白藜芦醇能够降低MMP-1、9的浓度,从而预防和延缓动脉硬化的发生。     

Non-invasive evaluation of carotid artery wall thickness using improved dynamic programming technique

An improved dynamic programming (DP) segmentation technique for detecting the intima-media layer of the far wall of the common carotid artery (CCA) of longitudinal and transversal ultrasound (US) images using optimal search technique is presented here. The algorithm is developed considering the normalization and smoothing for estimating the intima media thickness (IMT) of the normal and abnormal subjects. The segmentation features of different subjects obtained using the proposed technique have been compared with the manual measurements. The results show that an inter-observer error and a coefficient of variation are found as ±0.035 mm and 3.55%, respectively. The magnitudes of the IMT values have been used to explore the rate of prediction of blockage existing in the cerebrovascular and cardiovascular pathologies, and also hypertension and atherosclerosis.