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101.
脂蛋白相关磷脂酶A2 (lipoprotein- associated Phospholipase A2,Lp- PLA2)是磷脂水解酶超家族中的一员,能水解低密度脂蛋白中的氧化修饰磷脂,产生溶血卵磷脂和氧化性游离脂肪酸两种促炎介质。最近研究发现Lp- PLA2能够介导炎症反应以及促进动脉粥样硬化(atherosclerosis , AS)的形成,现已成为一个新炎性反应标志物和心血管事件的独立风险预示因子。针对这一动脉粥样硬化过程中的关键酶设计的抑制剂很多。其中Darapladib是目前最接近上市的一种Lp- PLA2特异性抑制剂,目前其Ⅲ期临床试验已完成。Darapladib作为一种新兴的抗AS分子靶点药物,受到人们广泛的关注。已有多项研究表明它能降低Lp- PLA2的活性,减轻炎症反应,从而控制AS的发展与恶化。本文综述了Lp- PLA2及其抑制剂Darapladib在AS中的作用机制以及近年来 Darapladib的药效学研究进展。 相似文献
102.
高脂血症对兔动脉壁一氧化氮系统的影响及药物的干预效果 总被引:3,自引:1,他引:3
将雄性纯种新西兰家兔36只随机分为三组,喂饲胆固醇形成实验性高胆固醇血症,部分加用麝香保心丸喂养;同时采用定量RT-PCR等技术,观察高脂血症对动脉壁一氧化氮系统代谢的影响,以及麝香保心丸的保护作用.结果表明:高脂饮食可造成动脉一氧化氮代谢的紊乱,降低动脉壁内皮型一氧化氮合酶(eNOS)基因的表达(P相似文献
103.
目的:观察小麦胚芽油(wheat germ oil,WGO)对动脉粥样硬化(atherosclerosis,AS)大鼠的治疗效果,并探讨其抗 AS 的可能作用机制。方法连续高脂乳剂灌胃4周,制作 AS 大鼠模型,分别给予各组大鼠连续灌胃不同剂量 WGO 8周;HE 染色光镜下观察大鼠主动脉弓病理形态的改变;酶联免疫吸附试验(ELISA)法检测各组大鼠血清中前列环素(Prostacyclin 2, PGI2)、血栓素 A2(Thromboxane 2,TXA2)及内皮素-1(Endothelin-1,ET-1)的含量。结果2.0 g·kg -1的 WGO 能明显改善 AS大鼠主动脉弓的病理状态,基本恢复正常状态;与模型组比较,1.0、2.0 g·kg -1 WGO 均可显著提高 AS 大鼠血清中 PGI2含量,明显降低 TXA2、ET-1水平(P <0.05)。结论WGO 能明显改善 AS 大鼠的动脉粥样硬化状态。其作用机制可能为小麦胚芽油具有良好的调节 PGI2、TXA2平衡,抑制血栓形成,修复内皮损伤以及较强的抗氧化作用。 相似文献
104.
Dragana Nikolic Manfredi Rizzo Dimitri P Mikhailidis Norman C Wong Maciej Banach 《Expert opinion on investigational drugs》2015,24(10):1389-1398
Introduction: RVX-208 is a first-in-class, orally active, novel small molecule in development by Resverlogix Corporation (Calgary, AB, Canada). It acts through an epigenetic mechanism by inhibiting the bromodomain and extraterminal (BET) family of proteins, increasing apolipoprotein A-I (apoA-I) and targeting high-density lipoprotein (HDL) metabolism, including generating of nascent HDL and increased larger HDL particles, resulting in the stimulation of reverse cholesterol transport. RVX-208 also has a beneficial effect on inflammatory factors known to be involved in atherosclerosis and plaque stability. New therapeutic strategies are needed for patients with atherosclerosis.Areas covered: In this review, the authors evaluate the use of RVX-208 as an agent for the treatment of atherosclerosis. The article is based on a literature search considering both animal and human studies available on PubMed as well as Media Releases from the Resverlogix Corporation.Expert opinion: The current evidence suggests promising beneficial effects of this novel drug in the prevention and treatment of atherosclerosis and other metabolic disorders. Its unique mechanism of action is encouraging; it affects several pathways and has a modest effect on HDL levels. There is also a shift in particle size to larger HDL particles, which may have potent atheroprotective effects. Future clinical development is needed, including safety assessment. 相似文献
105.
目的::探讨前部缺血性视神经病变( anterior ischemic optic neuropathy, AION)患者与颈动脉血管超声改变的关系。方法:对54例AION患者及同期进行健康体检者54例作为对照组,应用彩色超声诊断仪检测颈动脉超声影像学特征变化。结果:AION患者54例中38例出现颈动脉粥样硬化病变,占接受该项检查总数的70%,其中硬斑18例(33%),软斑13例(24%),混合斑7例(13%);对照组中检出粥样硬化20例,占接受该项检查总数的37%,其中硬斑12例(22%),软斑5例(9%),混合斑3例(6%);均未见颈动脉狭窄及明显流速改变。 AION患者组与对照组粥样硬化斑块的例数比较,差异有统计学意义(χ2=12.836,P=0.005)结论:AION的发生与颈动脉粥样硬化有相关性,颈动脉超声检查对查找AION的病因及诊断有重要的价值。 相似文献
106.
Correlation between osteocalcin‐positive endothelial progenitor cells and spotty calcification in patients with coronary artery disease 下载免费PDF全文
He Zhang Li‐jun Wang Dong‐lei Si Chuan Wang Jing‐ci Yang Ping Jiang Chao Du Jian‐jun Wang 《Clinical and experimental pharmacology & physiology》2015,42(7):734-739
Immature endothelial progenitor cells (EPC) carrying osteocalcin (OCN) might mediate vascUlar calcification in coronary artery disease (CAD). Spotty calcification within atherosclerotic plaque is associated with cardiovascular events. The aim of the present study was to assess the correlation between immature EPC levels and spotty calcification in CAD patients. In the 224 CAD patients studied, 76 had acute myocardial infarction (AMI), 102 had unstable angina pectoris (UAP), and 46 had stable angina pectoris (SAP). The levels of OCN‐positive (OCN+) EPC were analysed by flow cytometry. The status of spotty calcification was determined by cardiac computed tomography angiography. OCN+ EPC and calcium deposits were significantly increased in acute coronary artery syndrome (ACS) when compared with those in SAP patients. Positive correlation was also revealed between the number of OCN+ EPC and the frequency of spotty calcification and levels of serum high‐sensitivity C‐reactive protein (hs‐CRP) and serum alkaline phosphatase in AMI and UAP patients. In summary, the number of OCN+ EPC is positively related to the frequency of spotty calcification in ACS patients. Serum hs‐CRP and serum alkaline levels are thought to contribute to the elevation of OCN+ EPC. 相似文献
107.
Glucose inhibits replication of cultured human endothelial cells 总被引:5,自引:0,他引:5
R. W. Stout 《Diabetologia》1982,23(5):436-439
Summary Diabetes is an important risk factor for atherosclerosis but the mechanism of the risk is unknown. As endothelial injury is considered to be an early event in the development of atherosclerosis, the effect of glucose on endothelial cell replication was studied. Concentrations of glucose of 11.2, 16.8 and 22.4 mmol/l inhibited DNA synthesis in cultured human umbilical venous endothelial cells by 8.1±10.8, 24.3±8.8 and 30.9±7.4%, respectively. Glucose also inhibited the proliferative response of endothelial cells to experimental wounds in the cell layer. Sorbitol (22.4 mmol/l) inhibited endothelial cell DNA synthesis by 50±13.6%, but mannitol (22.4 mmol/l) inhibited DNA synthesis by only 3±24.3%. It is suggested that in diabetic subjects, high blood glucose levels may cause endothelial injury, or inhibit its repair, and hence allow the exposure of the arterial media to plasma and its constituents. 相似文献
108.
高同型半胱氨酸血症与不稳定斑块 总被引:11,自引:0,他引:11
血浆同型半胱氨酸的代谢异常导致的高同型半胱氨酸血症是动脉粥样硬化和冠心病的一个独立危险因素。针对高同型半胱氨酸与动脉粥样硬化和斑块稳定之间的确切联系,以及药物干预等问题成为研究的热点。现主要通过致炎症因子、氧化应激及内质网应激、免疫反应等多种细胞机制水平对同型半胱氨酸的作用作一综述。 相似文献
109.
Ku-Chung Chen Yi-Chu Liao Jaw-Yuan Wang Ying-Chu Lin Chung-Ho Chen Suh-Hang Hank Juo 《Oncotarget》2015,6(27):24105-24118
Hyperlipidemia, including the oxidized low-density lipoprotein (oxLDL) accumulation, is a risk and highly associated with the development of cancers and cardiovascular diseases. microRNA-210 (miR-210), a hypoxia-responsive microRNA regulated by HIF-1α, has been implicated in cancer and cardiovascular disease formation. Furthermore, Bioinformatics analysis revealed that the promoter of the miR-210 gene contains CpG-rich regions. It is unclear whether miR-210 expression could be epigenetically regulated in these disease progresses. The study aimed to explore the relationships between lipid and miR-210 in the context of cardiovascular disease and gastrointestinal cancer. We demonstrated oxLDL can decrease methylation in the miR-210 promoter to up-regulate miR-210. HIF-1α can bind to miR-210 promoter, but this HIF-1α binding site can be blocked by methylation. We showed that subjects of carotid atherosclerosis, stroke patients and cancer patients had hypomethylation in the miR-210 promoter, especially the HIF-1α binding site. Furthermore, miR-210 can directly inhibit sprouty-related EVH1 domain 2 (SPRED2) expressions, and SPRED2 reduces cell migration via ERK/c-Fos/MMPs pathways. Increased miR-210 and reduced SPRED2 levels were found in aorta of mice under high-fat diet and tumor tissues, which implied that miR-210 can be an underlying mechanism to explain oxLDL as a common risk factor for cardiovascular disease and gastrointestinal cancer. 相似文献
110.
颈动脉内膜-中膜厚度与缺血性脑血管病 总被引:4,自引:0,他引:4
颈动脉内膜-中膜厚度(IMT)是指颈动脉血管内膜和中膜之间的垂直距离。IMT增厚是动脉粥样硬化的早期表现。与缺血性脑血管病密切相关。也与多种血管危险因素有关,被认为是反映全身动脉粥样硬化性疾病的良好指标。临床上可借助超声检测颈动脉IMT来反映动脉粥样硬化的发生、发展或消退,并提供临床防治动脉粥样硬化的依据和疗效判断标准。 相似文献