oxLP(a)是脂蛋白(a)的致血管病变活性形式，预实验发现其可以焦亡的方式损伤血管内皮细胞(VEC)，但其机制未明。我们新近发现oxLP(a)可下调DNA去甲基化酶TET2和线粒体基因CYTB的表达诱生ROS，CYTB基因上有1个CG岛，故CYTB基因可能受TET2修饰调控。CYTB蛋白为呼吸链复合物Ⅲ的重要组份，参与电子传递。故提出oxLP(a)通过下调TET2导致CYTB基因甲基化修饰异常和表达水平下降，引起呼吸链复合物Ⅲ功能障碍诱生ROS，促进VEC焦亡和AS病变的假说。拟首先在人AS斑块上检测TET2-cytb-ROS途径上的关键节点分子，然后在apo-/-E小鼠动脉粥样硬化动物模型和VEC上，采用基因转染、免疫荧光、亚硫酸盐测序等现代分子病理技术，干预TET2、CYTB及ROS，分析AS、焦亡、线粒体功能，验证此途径，探索oxLP(a)致AS新机制、新模式，并提供新的干预靶点。

oxLP (a) is the active and pathogenesis form of lipoprotein (a) in the vascular diseases. In preliminary experience, oxLP(a) damage vascular endothelial cells (VEC) in the form of pyroptosis, while the mechanism is still not clear. We recently found that oxLP(a) down-regulate the expression of DNA demethylase TET2 and mitochondrial gene CYTB inducing ROS. There is a CG island on the CYTB gene, so the CYTB gene may be the target of TET2 modification. CYTB protein as an important content for the respiratory chain complex Ⅲ, involved in electron transfer. Therefore, oxLP (a) by down-regulating TET2 results in abnormal CYTB gene methylation modification and expression level decreased, cause the respiratory chain complexes Ⅲ dysfunction induce ROS, subsequently, promoting the VEC pyroptosis and AS lesions. We proposed to detect first the key node in progress of TET2-cytb-ROS in the human AS plaque. And, using gene transfection, immunofluorescence, sulfite sequencing and other modern molecular pathology, in the apo -/- E on animal models of atherosclerosis in mice and VEC, intervenes TET2， CYTB and ROS, analyzing the AS, pyroptosis, mitochondrial function. Therefore, exploring new mechanism and new pattern of oxLP (a) inducing pathological changes in AS, and providing new targets for intervention.