Natriuretic Peptides and Cell-based Therapy for Heart Failure

这一重新提交的项目的总体目标仍然是建立 一种基于细胞的技术，通过冠状动脉内输注表达脑利钠肽（BNP）的基因修饰的自体血液生长内皮细胞，在心力衰竭的狗模型中预防进行性左心室（LV）功能障碍。利钠肽系统（natriuretic peptide system，NPK）在心脏、肾脏和血管系统的体液整合中起着重要的生理作用，以控制钠平衡和动脉血压，并且有新的证据表明激活该系统是有益的。具体而言，它被认为是对LV功能障碍的代偿性内分泌反应，可维持钠平衡，而不会激活肾素-血管紧张素-醛固酮系统和增加充盈压。目前，BNP已被批准用于心力衰竭的IV使用，并且在欧洲正在进行临床试验，以研究内皮祖细胞（EPCs）在心肌缺血和非缺血性左心室（LV）功能障碍中的治疗作用。因此，这一应用？的意义在于，它使用有前途的细胞和遗传方法解决了一个重要的临床问题。

The overall objective of this resubmitted project remains focused on the establishment of a cell based technique to prevent progressive left ventricular (LV) dysfunction in a dog model of heart failure using an intracoronary infusion of genetically-modified autologous blood outgrowth endothelial cells that express brain natriuretic peptide (BNP). The natriuretic peptide system (NPS) plays an important physiological role in the humoral integration of the heart, kidney and vasculature to control sodium balance and arterial blood pressure, and there is emerging evidence that activation of this system is beneficial. Specifically, it is considered a compensatory endocrine response to LV dysfunction that maintains sodium balance without activating the renin-angiotensin-aldosterone system and increasing filling pressure. Presently, BNP has been approved for IV use in heart failure and there are clinical trials that are being conducted in Europe to investigate the therapeutic role of endothelial progenitor cells (EPCs) in myocardial ischemia and in nonischemic left ventricular (LV) dysfunction. Thus this application?s significance is that it addresses an important clinical problem using a promising cellular and genetic approach.