Platelets in vascular injury repair

项目摘要/摘要 经皮动脉介入治疗和动脉搭桥手术因血管内膜问题而复杂化。 增生(再狭窄)。糖尿病患者更有可能经历再狭窄，即使在药物洗脱后也是如此 支架。随着血管内手术(例如血管成形术和装置的插入)和 高度流行的心血管疾病的外科手术(例如搭桥)，修复的最佳解决方案 是必不可少的。动脉损伤后的修复过程是复杂的。损伤后开始修复的情况良好 研究血栓形成、炎症、细胞增殖和重塑。决议案 人们对修理过程知之甚少，尤其是什么构成了防止过度修理的“刹车”？ 血小板是抵御血管损伤的第一道重要防线，最初起到止血作用。 当被激活时，血小板也释放生物活性介质，如PDGF和血栓烷，促进 VSMC从静止的收缩表型去分化为高度合成和增殖的细胞 打字，促进损伤修复。过度修复，如糖尿病患者的内膜增生症 手术或血管干预后的糖尿病(DM)可由增强的VSMC脱分化和 扩散。我们将解决这样的假设，即水平转移血小板衍生的miRNAs到VSMC 提供一种新的机制来调节VSMC的表型转换，防止过度修复和 内膜增生症。我们处于一个独特的位置，可以用公认的外科手术来解决我们的假设 血管外科干预和血管平滑肌细胞生物学方面的专业知识(艾伦·达迪克医学博士和凯瑟琳·马丁博士)， 血小板专业知识(John Hwa MD博士，Wai Ho Tang博士)和糖尿病(Silvio Inzucchi MD， Raimund Herzog医学博士)。在短期内，我们将提出一种治疗血小板-VSMC的新机制 相互作用和动脉损伤修复。从长远来看，这些机械性的见解可能会提供新的 促进动脉损伤修复的治疗靶点。

PROJECT SUMMARY/ABSTRACT Percutaneous arterial interventions and arterial bypass surgeries are complicated by the problem of intimal hyperplasia (restenosis). Diabetic patients are more likely to experience restenosis, even after drug-eluting stents. With ever increasing numbers of intravascular (e.g. angioplasty and insertion of devices) and surgical procedures (e.g. bypass) for highly prevalent cardiovascular diseases, optimal resolution of repair is essential. The process of arterial repair after injury is complex. Initiation of repair after injury is well studied with thrombosis followed by inflammation, cellular proliferation and remodeling. Resolution of the repair process is poorly understood, particularly, what constitutes the “brake” to prevent excessive repair? Platelets provide a first and crucial line of defense against vascular injury, initially maintaining hemostasis. Upon activation, platelets also release bioactive mediators such as PDGF and thromboxane, promoting VSMC dedifferentiation from a quiescent contractile phenotype to a highly synthetic and proliferating cell type, promoting injury repair. Excessive repair, such as observed with intimal hyperplasia in diabetes mellitus (DM) after surgical or vascular interventions, can result from enhanced VSMC dedifferentiation and proliferation. We will address the hypothesis that horizontal transfer of platelet-derived miRNAs into VSMCs provide a novel mechanism for regulating VSMC phenotypic switching, preventing excessive repair and intimal hyperplasia. We are in a unique position to address our hypothesis with recognized surgical expertise in vascular surgical interventions and VSMC biology (Alan Dardik MD and Kathleen Martin PhD), platelet expertise (John Hwa MD PhD, Wai Ho Tang PhD), and diabetes mellitus (Silvio Inzucchi MD, Raimund Herzog MD). In the short term we will have presented a novel mechanism for platelet-VSMC interaction and arterial injury repair. In the long term, these mechanistic insights may provide new therapeutic targets in promoting arterial injury repair.