Molecular Mechanisms of Arterigenesis

本项目的总体目标是了解分子调控机制 动脉生成可作为血管闭塞性心血管疾病的潜在治疗手段 疾病包括冠心病、外周动脉疾病和脑血管疾病 疾病。我们已经组建了一支由高度熟练的PI组成的多学科团队，拥有不同的 研究背景(心脏病学、细胞生物学、生物机械工程学、药理学) 导致动脉血管系统发育和生长的关键分子事件。深入了解 对这些机制的理解可以解释为小说的发展 这一重要的心血管疾病的治疗方式。共同努力，我们的研究 将定义导致动脉血管生长的关键事件，并将导致 新疗法。 PPG目标是： 目的1.阐明ERK信号如何控制动脉形成(项目1)。 目的2.揭示miR 17-92簇在控制动脉形成中的作用及其 调节和与ERK信号的相互作用(项目2 目的3.确定流体剪切力和细胞外基质的变化如何激活 ERKs和其他介导动脉形成和识别限制的信号通路 疾病中损害动脉生成的点(项目3)。 与公众健康相关：冠状动脉疾病和外周动脉疾病是主要疾病 发达国家的疾病和死亡原因。动脉生成不良是导致 这些疾病以及在心肌梗死后患者的康复中。此应用程序建议 阐明调控血流依赖性血管重塑的信号网络和测试2 改善动脉生成的新方向。这些研究包括测试激活一种 动脉生成信号通路改善疾病模型中的动脉生成。他们有 有潜力确定治疗的新靶点和新试剂，以及实现更深层次的 对基础生物学的理解将成为未来研究的基础。

The overall goal of this Program Project is to understand molecular mechanisms regulating arteriogenesis that may be exploited as potential treatments for vasoocclusive cardiovascular diseases including coronary artery disease, peripheral arterial disease and cerebrovascular disease. We have assembled a multidisciplinary team of highly accomplished PIs with diverse backgrounds (cardiology, cell biology, biomechanical engineering, pharmacology) to investigate key molecular events that lead to development and growth of arterial vasculature. The in-depth understanding of these mechanisms can then be parlayed into development of novel therapeutic modalities for this important group of cardiovascular diseases. Together, our studies will define the key events leading to arterial vessel growth and will lead to the development of new therapies. PPG Aims are: Aim 1. Elucidate how ERK signaling controls arteriogenesis (Project 1). Aim 2. Unravel the role of the miR 17-92 cluster in controlling arteriogenesis and its regulation and interaction with ERK signaling (Project 2 Aim 3. Determine how fluid shear stress and changes in the extracellular matrix activate ERKs and other signaling pathways that mediate arteriogenesis, and identify restriction points that impair arteriogenesis in disease (Project 3). Relevance to Public Health: Coronary artery disease and peripheral artery disease are major causes of illness and death in developed nations. Poor arteriogenesis is a critical determinant of these diseases and in patients’ recovery after myocardial infarction. This application proposes to elucidate the signaling network that governs flow-dependent vessel remodeling and test two new directions for improving arteriogenesis. These studies include testing whether activating an arteriogenic signaling pathway improves arteriogenesis in disease models. They have the potential to identify new targets and new reagents for therapy, as well as to achieve a deeper understanding of the fundamental biology that will form the basis for future studies.