APOPTOTIC CASCADE IN ATHEROSCLEROSIS

动脉粥样硬化中的细胞凋亡级联

• 批准号: 2446568
• 负责人: Yong-Jian Geng
• 金额: $ 10.02万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2446568
• 关键词: CD95 molecule; actins; apoptosis; atherosclerosis; cell proliferation; cysteine endopeptidases; cytoskeleton; enzyme activity; gelsolin; human tissue; immunocytochemistry; laboratory mouse; tissue /cell culture; vascular endothelium

DESCRIPTION (Adapted from Investigator's Abstract): Apoptosis occurs in advanced human and experimental atherosclerosis, but little is known about the role of apoptosis in determination of the cellularity of arteries with early atherosclerotic lesion or fatty streaks. This application proposes that apoptosis represents a mechanism for eliminating cells from the intima, and that vascular cells undergo apoptosis following exposure to cytokines produced by T cells and macrophages which are also present in the lesion. It is further proposed that this is mediated by the Fas death signaling pathway and the ICE protease family. Specific Aim 1 will examine the balance between apoptosis and cell proliferation in arterial samples collected in the PDAY program by immunohistochemistry. Specific Aim 2 will examine expression of Fas, Fas ligand, and ICE-related proteases in smooth muscle cells undergoing apoptosis in atherosclerotic lesions and in cultured cells. Specific Aim 3 will examine the function of fragments of actin an gelsolin in mediating apoptosis. Arteries from mice deficient in expression of functional Fas (MRC/lpr/lpr) or gelsolin will be examined.

描述（改编自研究者摘要）：细胞凋亡发生在 晚期人类和实验性动脉粥样硬化，但人们对此知之甚少 细胞凋亡在动脉细胞结构测定中的作用 早期动脉粥样硬化病变或脂肪条纹。 本申请提出 细胞凋亡代表了一种从内膜消除细胞的机制， 血管细胞在暴露于细胞因子后会发生凋亡 由病变中也存在的 T 细胞和巨噬细胞产生。 进一步提出这是由 Fas 死亡信号介导的 途径和 ICE 蛋白酶家族。 具体目标 1 将检查 动脉样本中细胞凋亡和细胞增殖之间的平衡 通过免疫组织化学在 PDAY 程序中收集。 具体目标 2 将 检查平滑肌细胞中 Fas、Fas 配体和 ICE 相关蛋白酶的表达 动脉粥样硬化病变和培养物中发生凋亡的肌细胞 细胞。 具体目标 3 将检查肌动蛋白片段的功能 凝溶胶蛋白介导细胞凋亡。 来自表达缺陷小鼠的动脉 将检查功能性 Fas (MRC/lpr/lpr) 或凝溶胶蛋白的功能。

项目成果

Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line.

在源自人外周单核细胞和 THP-1 单核细胞系的巨噬细胞中，IL-6 对 A 类巨噬细胞清道夫受体的转录抑制作用。

• DOI: 10.1161/01.atv.19.8.1872
• 发表时间: 1999
• 期刊: Arteriosclerosis, thrombosis, and vascular biology
• 作者: Liao,HS;Matsumoto,A;Itakura,H;Doi,T;Honda,M;Kodama,T;Geng,YJ
• 通讯作者: Geng,YJ