Genetic analysis of molecular mechanisms of foam cell formation in atherosclerosis

在巨噬细胞中，NCEH1在适宜的中性pH下对胆固醇酯水解酶起主要作用。基因敲除研究表明NCEH1与泡沫细胞的形成和动脉粥样硬化的发展有很深的关系。此外，使用酶抑制剂的实验表明，NCEH1可能是人巨噬细胞中的主要酶，免疫组织化学分析表明NCEH1存在于抗CD68抗体染色的主动脉区域。此外，氧化甾醇可以增强NCEH1缺失的泡沫细胞的凋亡诱导作用，并促进动脉粥样硬化病变的严重程度。NCEH1是了解动脉粥样硬化发病机制以及指导临床应用包括其诊断和治疗的关键分子。

NCEH1 plays a principal role for cholesteryl ester hydrolase at optimal neutral pH in macrophages. Gene-knockout studies revealed that NCEH1 would have a deep relationship with foam cell formation and atherosclerotic development. In addition, it is suggested by experiments using the enzymatic inhibitor that NCEH1 might be a main enzyme in human macrophages and immunohistochemical analyses demonstrate that NCEH1 exists in the aortic area stained by anti-CD68 antibody. Furthermore oxysterols could augment the induction of apoptosis in foam cells lacking NCEH1 and advance the severity of atherosclerotic lesions. NCEH1 is a key molecule to understand the pathogenesis of atherosclerosis and lead to clinical applications including its diagnosis and treatment.