APOPTOTIC CASCADE IN ATHEROSCLEROSIS

描述(摘自《调查者摘要》)：细胞凋亡发生在 晚期人类和实验性动脉粥样硬化，但对此知之甚少 细胞凋亡在动脉粥样硬化性心脏病中的作用 早期动脉粥样硬化病变或脂肪条纹。此应用程序建议 细胞凋亡代表了一种清除血管内膜细胞的机制， 而血管细胞在暴露于细胞因子后会发生凋亡 由T细胞和巨噬细胞产生，这些细胞也存在于病变中。 进一步提出，这是通过Fas死亡信号来调节的 途径和ICE蛋白水解酶家族。《特定目标1》将考察 动脉标本中细胞凋亡与细胞增殖的平衡 免疫组织化学方法收集于PDAY程序中。特定目标2将 检测Fas、Fas配体和ICE相关蛋白在Smooth中的表达 动脉粥样硬化病变和培养的肌细胞发生凋亡 细胞。特指目标3将研究肌动蛋白片段的功能 明胶蛋白在介导细胞凋亡中的作用。表达缺失的小鼠动脉 对功能性Fas(MRC/LPR/LPR)或明胶进行检测。

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.