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1.
理论上认为胆固醇逆向转运的速率与动脉粥样硬化程序呈负相关。但目前尚无完善的测试血浆脂蛋白-胆固醇体内代谢的方法。我们运用同位素^3H-胆固醇示踪方法,建立房室模型,选取健康兔与AS兔对照,研究血浆脂蛋白转运胆固醇能力的差异,并结合AS兔主动脉斑块程度对比,结果验证了上述理论,此法如改用短半衰期同位素或稳定性同位素标记的胆固醇,就可用于人体,这可为临床判断AS程度提供一种无创性的新方法。  相似文献   
2.
With unique characteristics such as high surface area, capacity of various functionalization, low weight, high conductivity, thermal and chemical stability, and free radical scavenging, carbon nanomaterials (CNMs) such as carbon nanotubes (CNTs), fullerene, graphene (oxide), carbon nanohorns (CNHs), and their derivatives have increasingly been utilized in nanomedicine and biomedicine. On the one hand, owing to ever-increasing applications of CNMs in technological and industrial fields as well as presence of combustion-derived CNMs in the ambient air, the skepticism has risen over the adverse effects of CNMs on human being. The influences of CNMs on cardiovascular system and cardiovascular diseases (CVDs) such as atherosclerosis, of which consequences are ischemic heart disease and ischemic stroke, as the main causes of death, is of paramount importance. In this regard, several studies have been devoted to specify the biomedical applications and cardiovascular toxicity of CNMs. Therefore, the aim of this review is to specify the roles and applications of various CNMs in atherosclerosis, and also identify the key role playing parameters in cardiovascular toxicity of CNMs so as to be a clue for prospective deployment of CNMs.  相似文献   
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The major function of the Haptoglobin (Hp) protein is to control trafficking of extracorpuscular hemoglobin (Hb) thru the macrophage CD163 receptor with degradation of the Hb in the lysosome. There is a common copy number polymorphism in the Hp gene (Hp 2 allele) that has been associated with a severalfold increased incidence of atherothrombosis in multiple longitudinal studies. Increased plaque oxidation and apoptotic markers have been observed in Hp 2-2 atherosclerotic plaques, but the mechanism responsible for this finding has not been determined. We proposed that the increased oxidative injury in Hp 2-2 plaques is due to an impaired processing of Hp 2-2-Hb complexes within macrophage lysosomes, thereby resulting in redox active iron accumulation, lysosomal membrane oxidative injury, and macrophage apoptosis. We sought to test this hypothesis in vitro using purified Hp-Hb complex and cells genetically manipulated to express CD163. CD163-mediated endocytosis and lysosomal degradation of Hp-Hb were decreased for Hp 2-2-Hb complexes. Confocal microscopy using lysotropic pH indicator dyes demonstrated that uptake of Hp 2-2-Hb complexes disrupted the lysosomal pH gradient. Cellular fractionation studies of lysosomes isolated from macrophages incubated with Hp 2-2-Hb complexes demonstrated increased lysosomal membrane oxidation and a loss of lysosomal membrane integrity leading to lysosomal enzyme leakage into the cytoplasm. Additionally, markers of apoptosis, DNA fragmentation, and active caspase 3 were increased in macrophages that had endocytosed Hp 2-2-Hb complexes. These data provide novel mechanistic insights into how the Hp genotype regulates lysosomal oxidative stress within macrophages after receptor-mediated endocytosis of Hb.  相似文献   
5.
Recent genome-wide association studies have identified single-nucleotide polymorphism (SNPs) within the SLC22A3 (solute carrier family 22 member 3) gene associated with coronary heart disease (CHD) in the Caucasian population. We performed molecular analysis to investigate the potential role of SLC22A3 variants in CHD. Our study showed that the common polymorphism rs3088442 G→A, which is localized in the 3′ UTR of the SLC22A3 gene, was associated with a decreased risk of CHD in the Chinese population by a case control study. In silico analysis indicated that G→A substitution of SNP rs3088442 created a putative binding site for miR-147 in the SLC22A3 mRNA. By overexpressing miR-147 or inhibiting endogenous miR-147, we demonstrated that SNP rs3088442 G→A recruited miR-147 to inhibit SLC22A3 expression. Moreover, SLC22A3 deficiency significantly decreased LPS-induced monocytic inflammatory response by interrupting NF-κB and MAPK signaling cascades in a histamine-dependent manner. Notably, the expression of SLC22A3A was also suppressed by LPS stimulus. Our findings might indicate a negative feedback mechanism against inflammatory response by which SLC22A3 polymorphisms decreased the risk of CHD.  相似文献   
6.
Low density lipoproteins activate phosphoinositide turnover, increase free cytoplasmic calcium concentration and stimulate phosphorylation of 20- and 47-kDa proteins in blood platelets. All these effects are substantially potentiated by epinephrine.  相似文献   
7.
Atherosclerosis is a chronic inflammatory disease of the artery wall, and both innate and adaptive immunity play important roles in the pathogenesis of this disease. In several experimental and human experiments of early atherosclerotic lesions, it has been shown that the first pathogenic event in atherogenesis is intimal infiltration of T cells at predilection sites. These T cells react to heat shock protein 60 (HSP60), which is a ubiquitous self-antigen expressed on the surface of endothelial cells (ECs) together with adhesion molecules in response to classical risk factors for atherosclerosis. When HSP60 is expressed on the EC surface, it can act as a “danger-signal” for both cellular and humoral immune reactions. Acquired by infection or vaccination, beneficial protective immunity to microbial HSP60 and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. Thus, the development of atherosclerosis during aging is paid by the price for lifelong protective preexisting anti-HSP60 immunity by harmful (auto)immune cross-reactive attack on arterial ECs maltreated by atherosclerosis risk factors. This is supported by experiments, which shows that bacterial HSP60 immunization can lead and accelerate experimental atherosclerosis. This review article presents accumulating proof that supports the idea that tolerization with antigenic HSP60 protein or its peptides may arrest or even prevent atherosclerosis by increased production of regulatory T cells and/or anti-inflammatory cytokines. Recent data indicates that HSP60, or more likely some of its derivative peptides, has immunoregulatory functions. Therefore, these peptides may have important potential for being used as diagnostic agents or therapeutic targets.  相似文献   
8.
PurposeAccurate determination of the bifurcation angle and correlation with plaque buildup may lead to the prediction of coronary artery disease (CAD). This work evaluates two techniques to measure bifurcation angles in 3D space using coronary computed tomography angiography (CCTA).Materials and MethodsNine phantoms were fabricated with different bifurcation angles ranging from 55.3° to 134.5°. General X-ray and CCTA were employed to acquire 2D and 3D images of the bifurcation phantoms, respectively. Multiplanar reformation (MPR) and volume rendering technique (VRT) were used to measure the bifurcation angle between the left anterior descending (LAD) and left circumflex arteries (LCx). The measured angles were compared with the true values to determine the accuracy of each measurement technique. Inter-observer variability was evaluated. The two techniques were further applied on 50 clinical CCTA cases to verify its clinical value.ResultsIn the phantom setting, the mean absolute differences calculated between the true and measured angles by MPR and VRT were 2.4° ± 2.2° and 3.8° ± 2.9°, respectively. Strong correlation was found between the true and measured bifurcation angles. Furthermore, no significant differences were found between the bifurcation angles measured using either technique. In clinical settings, large difference of 12.0° ± 10.6° was found between the two techniques.ConclusionIn the phantom setting, both techniques demonstrated a significant correlation to the true bifurcation angle. Despite the lack of agreement of the two techniques in the clinical context, our findings in phantoms suggest that MPR should be preferred to VRT for the measurement of coronary bifurcation angle by CCTA.  相似文献   
9.
Subendothelial retention of lipoproteins by proteoglycans (PGs) is the initiating event in atherosclerosis. The elongation of chondroitin sulfate (CS) chains is associated with increased low-density lipoprotein (LDL) binding and progression of atherosclerosis. Recently, it has been shown that 2 Golgi enzymes, chondroitin 4-O-sulfotransferase-1 (C4ST-1) and chondroitin N-acetylgalactosaminyltransferase-2 (ChGn-2), play a critical role in CS chain elongation. However, the roles of C4ST-1 and ChGn-2 during the progression of atherosclerosis are not known. The aim of this study was to analyze the expression of C4ST-1 and ChGn-2 in atherosclerotic lesions in vivo and determine whether their expression correlated with CS chain elongation.Low-density lipoprotein receptor knockout (LDLr KO) mice were fed a western diet for 2, 4, and 8 weeks to stimulate development of atherosclerosis. The binding of LDL and CS PG in this mouse model was confirmed by chondroitinase ABC (ChABC) digestion and apolipoprotein B (apo B) staining. Gel filtration analysis revealed that the CS chains began to elongate as early as 2 weeks after beginning a western diet and continued as the atherosclerosis progressed. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) showed that the mRNA levels of C4ST-1 and ChGn-2 increased after 8 weeks of this diet. In contrast, the mRNA levels of their homologs, C4ST-2 and ChGn-1, were unchanged. In addition, immunohistochemical analysis demonstrated that the expression of C4ST-1 and ChGn-2 appeared to have similar site-specific patterns and coincided with biglycan expression at the aortic root.Our results suggested that C4ST-1 and ChGn-2 may be involved in the elongation of CS chains in the arterial wall during the progression of atherosclerosis. Therefore, modulating their expression and activity might be a novel therapeutic strategy for atherosclerosis.  相似文献   
10.
目的:观察他汀类调脂药物瑞舒伐他汀(Rosuvastatin)对2型糖尿病(type2diabetesmellitus,T2DM)大鼠早期动脉粥样硬化形成的影响,并探讨其可能的机制。方法:将45只雄性SD大鼠随机分为正常对照组(NC组)、2型糖尿病组(DM组)、2型糖尿病瑞舒伐他汀治疗组(DR组),每组15只。以喂高糖高脂饮食方法建立SD大鼠糖尿病模型,DM组、DR组给予高糖高脂饮食1个月后腹腔注射25mg/kg链脲佐菌素;NC组给予普通饮食,注射枸橼酸缓冲液作为对照。在此基础上,DR组给予瑞舒伐他汀5mg/(kg.d)灌胃,NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平与稳态血糖(BG)、稳态胰岛素(PGI)浓度,用免疫组化法检测主动脉血管壁白细胞分化抗原40(clusterofdifferentiation 40,CD40)及基质金属蛋白酶-2(MMP-2)、激活蛋白-1(activator protein-1,AP-1)的表达水平。结果:DM组、DR组TC、TG、LDL-C与BG水平较NC组均显著升高(F=33.71~426....  相似文献   
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