Genetic analysis of molecular mechanisms of foam cell formation in atherosclerosis

动脉粥样硬化泡沫细胞形成分子机制的遗传分析

• 批准号: 23591339
• 负责人: OSUGA JUN-ICHI
• 金额: $ 3.41万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591339/
• 关键词: マクロファージ; コレステロールエステル; 泡沫化; 粥状動脈硬化症

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.

NCEH1在巨噬细胞中的最佳中性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NCEH 1可能是人巨噬细胞中的主要酶，免疫组织化学分析表明NCEH 1存在于抗CD 68抗体染色的主动脉区域。 此外，氧化固醇可增强NCEH 1缺失的泡沫细胞的凋亡诱导，并使动脉粥样硬化病变的严重程度增加。 NCEH1是了解动脉粥样硬化发病机制的关键分子，并导致其诊断和治疗等临床应用。

项目成果

Apolipoprotein C-II deficiency with no rare variant in the APOC2 gene.

载脂蛋白 C-II 缺陷，APOC2 基因无罕见变异。

• 发表时间: 2013
• 期刊: J. Atheroscler. Thromb.
• 作者: Takase S;Osuga J;Fujita H;Hara K;Sekiya M;Igarashi M;Takanashi M;Takeuchi Y;Izumida Y;Ohta K;Kumagai M;Nishi M;Kubota M;Masuda Y;Taira Y;Okazaki S;Iizuka Y;Yahagi N;Ohashi K;Yoshida H;Yanai H;Tada N;Gotoda T;Ishibashi S;Kadowaki T,
• 通讯作者: Kadowaki T,

Suppression of the Pancreatic Duodenal Homeodomain Transcription Factor-1 (Pdx-1) Promoter by Sterol Regulatory Element-binding Protein-1c (SREBP-1c)

• DOI: 10.1074/jbc.m110.186221
• 发表时间: 2011-08-12
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Amemiya-Kudo, Michiyo;Oka, Junko;Shimano, Hitoshi
• 通讯作者: Shimano, Hitoshi

Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement

• DOI: 10.1016/j.bbrc.2010.11.103
• 发表时间: 2011-01-07
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Ohta, Keisuke;Sekiya, Motohiro;Osuga, Jun-ichi
• 通讯作者: Osuga, Jun-ichi

Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesteryl ester transfer protein in type 2 diabetes mellitus.

Ezetimibe 是一种 Niemann-Pick C1-like 1 蛋白抑制剂，可降低 2 型糖尿病中的胆固醇酯转移蛋白。

• 发表时间: 2012
• 期刊: Endocrine journal
• 影响因子: 2
• 作者: H. Yagyu;Shuichi Nagashima;Manabu Takahashi;Michiaki Miyamoto;K. Okada;J. Osuga;S. Ishibashi
• 通讯作者: S. Ishibashi

Current smoking status may be associated with overt albuminuria in female patients with type 1 diabetes mellitus: a cross-sectional study.

• DOI: 10.1186/1617-9625-10-12
• 发表时间: 2012-08-10
• 期刊: Tobacco induced diseases
• 影响因子: 3.7
• 作者: Okada K;Osuga J;Kotani K;Yagyu H;Miyamoto M;Nagasaka S;Ishibashi S
• 通讯作者: Ishibashi S