OCC不稳定斑块课件.pptVIP

惠汝太 心内科教授，高血压中心主任 遗传学教授，中-德分子医学室主任 教育部心血管基因与临床重点室 科技部/国家外专局国际合作基地 中国医学科学院/北京协和医学院 阜外医院 Hui Rutai MD PhD Beijing FuWai Hospital Chinese Academy of Medical Sciences;Interest Conflict Disclosure;Major clinical complications of atherosclerosis arise when atherosclerotic lesions evolve into complex, unstable forms characterized by a thin fibrous cap, a large lipid-filled necrotic core and an accumulation of macrophages. These ‘vulnerable’ plaques are prone to rupture, which can then trigger acute unstable coronary artery syndromes and ischemic strokes. ;不稳定斑块的识别;一，不稳定斑块识别的有创影像学技术;;ACS多发生于中小斑块和偏心斑块;;二，生物标记（9项标记预测）;三，基因变异;VKORC1－Vitamin K Epoxide ReductaseComplex subunit1蛋白和基因;分子特征;163aa；分子量 18kD，染色体定位 16p11.1 一个可切的信号肽？ N端糖基化位点 蛋白激酶 C 磷酸化位点，酪氨酸激酶磷酸化位点 内质网膜储留信号: KKXX-like motif in the C-terminus: KAKR ;没有明显的传统功能结构域No conserved domain;组织表达谱;VKORC1定位在血管内膜，在内皮细胞中表达;Realtime-PCR 分析VKORC1的表达;VKORC1参与血管生成－微管形成实验;结 论 ;γcarboxylase; 第一类：与凝血相关的: 表达异常引起血栓形成 第二类：与骨骼钙化有关的：可以导致血管钙化 这些蛋白的激活与功能与这些蛋白的羧化有关。 Matrix gla protein (MGP) is a protein found in numerous body tissues that requires vitamin K for its optimum function. It is present in bone (together with the related vitamin K-dependent protein osteocalcin), as well as in heart, kidney and lung. In bone, its production is increased by vitamin ;Common polymorphisms in the VKORC1 gene have been found in warfarin-resistant patients to affect warfarin dose and then blood clotting. 预测疗效与副作用 ;;研究假设：动脉硬化=血栓形成 +血管钙化（动脉硬 化）；We hypothesized that variation of VKORC1 gene could change the Gla or calcification of the proteins-related to coagulation and vascular calcification, and then vascular disease risk. 编码Vit-K依赖的蛋白基因变异会造成动脉硬化斑块 不稳定,因为此类蛋白涉及血栓与动脉硬化。 我们的假设在病例对照研究中验证。 ;;;;;Circulatio