Myocardial ischemia protection by HO-1 gene delivery

HO-1 基因传递的心肌缺血保护

• 批准号: 6622352
• 负责人: Alok Pachori
• 金额: $ 4.64万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622352
• 关键词: cardiovascular disorder prevention; cardiovascular disorder therapy; cytoprotection; enzyme therapy; gene delivery system; gene therapy; heme oxygenase; laboratory rat; myocardial infarction; myocardial ischemia /hypoxia; nonhuman therapy evaluation; oxidative stress; postdoctoral investigator; reperfusion

DESCRIPTION (provided by applicant): Myocardial ischemia causes inflammatory response, reduced cardiac function and irreversible cell death. Formation of reactive oxygen species (ROS) upon reperfusion of the ischemic area augments the ischemic insult. Injured cells respond to this insult by activating heme oxygenase-1 (HO-1) enzyme, which provides cytoprotective effects. Recent evidence has shown that prior induction of HO-1 protects tissues against ischemia/reperfusion (I/R) mediated injury and prolongs tissue viability. Therefore it is possible that targeted overexpression of HO-1 under non-stressful conditions will protect against future insult and provide further understanding of HO-1?s protective mechanisms. We have recently developed an adeno-associated viral vector system to deliver human HO-1 (hHO-1) directly in the rat heart and have observed long term expression of the transgene and reduction in infarct size with a single treatment of the viral vector in a coronary artery ligation (LAD) model of ischemia/reperfusion. This proposal will test the hypothesis that intracardiac delivery of hHO-1 will result in long term transcription and translation of hHO-1, provide cytoprotective effects improve cardiac hemodynamics and reduce overall mortality in LAD model of I/R injury.

描述（由申请人提供）：心肌缺血引起炎症 反应、心脏功能下降和不可逆的细胞死亡。的形成 缺血区再灌注时活性氧（ROS）增加 缺血性损伤。受伤的细胞通过激活血红素来应对这种侮辱 oxygenase-1 (HO-1) 酶，提供细胞保护作用。最近的 有证据表明，预先诱导 HO-1 可以保护组织免受 缺血/再灌注（I/R）介导的损伤并延长组织活力。 因此，HO-1 的靶向过表达可能是在 无压力的条件将防止未来的侮辱并提供进一步的帮助 了解 HO-1 的保护机制。我们最近开发了一个 腺相关病毒载体系统可直接递送人 HO-1 (hHO-1) 大鼠心脏并观察到转基因的长期表达 通过病毒载体的单次治疗减少梗塞面积 冠状动脉结扎（LAD）缺血/再灌注模型。这个提议 将检验 hHO-1 心内递送将导致的假设 hHO-1 的长期转录和翻译，提供细胞保护作用 在 LAD 模型中改善心脏血流动力学并降低总体死亡率 I/R 损伤。