Development of Molecular Biologic Diagnostic and Therapeutic Method of Asymptomatic Myocardial Ischemia and Unstable Angina

无症状心肌缺血及不稳定型心绞痛分子生物学诊断及治疗方法的进展

基本信息

批准号：
07557231
负责人：
SEKO Yoshinori
金额：
$ 1.92万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

1. Molecular mechanism of cardiac adaptation to hypoxia/re oxygenation : We showed that hypoxia/re oxygenation activated Src family tyrosine kinases, p2l^<TAS>, three MAPK family member kinases and their upstream as well as downstream kinases, Jak/STAT tyro sine kinases, and a transcription factor ATF-2. The signal transduction cascades activated by these stimuli were at least partly different. 2. Autocrine mechanism via certain humoral factors involved in the activation of intracellular signaling induced by hypoxia/re oxygenation : (A) We showed that the activation of intracellular signaling in cardiac myocytes induced by hypoxia was mediated by VEGF in an auto crine fashion. (B) We found that similar autocrine mechanism was involved in the activation of intracellular signaling in cardiac myocytes induced by reoxygenation, and we are now isolating and purifying the humoral factor. 3. Sensitive detection of hypoxia/re oxygenation in the heart of patients with angina pectoris and acute myocardial infarction : (A) By measuring the serum levels of VEGF in patients with acute myocardial infarction undergoing early reperfusion therapy, we demonstrated that VEGF could be a sensitive indicator of ischemic (hypoxic) state. This also strongly supported the data of 2. (A). (B) We are now isolating and purifying the humoral factor involved in the activation of intracellular signaling induced by reoxygenation, and we suppose that the serum levels of the humaral factor will be a good indicator of reperfused (reoxygenated) state in the heart of these patients. 4. Anti-cell-adhesion molecule therapy against myocardial ischemia/reperfusion injury : We demonstrated using a rat model that in vivo administration of selectin oligopeptide or anti-sialy-Lewis^x mAb significantly reduced myocardial ischemia/reperfusion injury.

1。心脏适应低氧/氧合的分子机制：我们表明缺氧/RE氧合激活了SRC家族酪氨酸激酶，P2L^<TAS>，三个MAPK家族成员激酶及其上游，下游激酶以及下游激酶，Jak/Stat Tyro Sine Kinase asine Kinases and Transcription and Criptionals和A atf。这些刺激激活的信号转导级联反应至少部分不同。 2。通过缺氧/RE氧合引起的细胞内信号传导涉及的某些体液因子的自分泌机制：（a）我们表明，由低氧引起的心肌细胞中细胞内信号传导的激活是由VEGF介导的。（b）我们发现类似的自分泌机制参与了通过氧合诱导的心肌细胞中细胞内信号传导的激活，现在我们正在隔离和净化体液因子。 3。在心绞痛和急性心肌梗死患者心脏中缺氧/RE氧合的敏感检测：（a）通过测量急性心肌梗死患者接受早期再灌注疗法的VEGF的血清VEGF水平，我们证明VEGF可以证明VEGF可以表明VEGF是粘液性（低氧）的敏感指标）。这也强烈支持2。（a）的数据。（b）我们现在正在隔离和净化与重氧诱导的细胞内信号传导激活相关的体液因子，并且我们假设荷马尔因子的血清水平将是这些患者心脏中养殖（重氧）状态的良好指标。 4。针对心肌缺血/再灌注损伤的抗细胞粘附分子疗法：我们使用大鼠模型证明，该模型在体内施用Selectin寡肽或抗杀菌性LEWIS^X MAB显着降低了心肌缺血/再灌注损伤。