How inflammation and thrombosis fuel disease and aging: Focus on NETs

炎症和血栓如何加剧疾病和衰老：关注网络 此R35 0IA应用程序是基于最近资助的两个NHLBI RO1的扩展 题为《血栓形成和炎症反应中的英语教师》和《英语教师及其 调节与年龄相关的炎症性疾病中的酶。多年来，我们一直在 进行了一项成功的研究血栓形成和炎症的研究计划。我们的 目前的重点是新发现的中性粒细胞胞外陷阱(Net)。vt.在.的基础上 中性粒细胞激活，肽基精氨酸脱亚胺酶4(PAD4)转位到细胞核 以瓜氨酸化组蛋白。这会使染色质解聚，染色质以Net的形式释放。篮网 但我们已经展示了Net的阴暗面，即它们促进血栓形成， 炎症和与年龄相关的心肺纤维化。我们的核心假设是 节目内容有：网民参与形成稳定的有组织的和 血栓形成和网状破裂是溶栓所必需的。 血栓形成促进Net在邻近血管壁上沉积，也可在 远隔器官导致血栓后综合征和全身性 促凝剂和促炎状态。衰老促进网状结构的形成 网络反过来又会加剧慢性炎症和血栓形成疾病。我们相信 对蚊帐形成或销毁过程的抑制将是 对主人有利。最后，我们假设调控蚊虫增多症的基因，如 作为多肽精氨酸脱亚胺酶4(PAD4)，影响衰老。 瓦格纳实验室的工作被认为是创新和扎实的；客观的衡量标准 就是它的高引用率。该实验室一直由不止一项NHLBI拨款资助， 在15年的时间里，我也是一家大型PPG的输血生物学专业的PI。然而，在 最近的资金困难时期，我花了太多的时间来争取对我的 一群人。获得长期资助将使我腾出时间进行更多的指导、写作 复习和大学活动。此外，我们现在研究慢性炎症 疾病及其对衰老的影响。这些实验需要时间和更长的时间 支持的持续时间将确保我们能够有效地进行这项现有的研究。

How inflammation and thrombosis fuel disease and aging: Focus on NETs This R35 0IA application is an extension based on two recently funded NHLBI RO1 grants entitled “NETS in thrombosis and inflammatory responses” and “NETs and their modulating enzymes in age-related inflammatory diseases.” For many years, we have conducted a successful research program studying thrombosis and inflammation. Our current emphasis is on newly discovered neutrophil extracellular traps (NETs). Upon neutrophil activation, peptidylarginine deiminase 4 (PAD4) translocates to the nucleus to citrullinate histones. This decondenses chromatin, which is released as NETs. NETs trap microbes but we have shown a dark side of NETs, i.e., they promote thrombosis, inflammation and age-related heart and lung fibrosis. The central hypotheses of our program are: NETs are involved in the formation of a stable organized and vascularized thrombus and breaking up NETs is necessary for thrombolysis. Thrombosis promotes deposition of NETs in the adjacent vessel wall and also in distant organs leading to post-thrombotic syndrome and an increased systemic pro-coagulant and pro-inflammatory state. Aging promotes NET formation and NETs in turn escalate chronic inflammatory and thrombotic diseases. We believe that inhibition of the process of NET formation or destruction of NETs would be beneficial to the host. Finally, we hypothesize that genes regulating NETosis, such as peptidylarginine deiminase 4 (PAD4), impact aging. The work by the “Wagner Lab” is considered innovative and solid; an objective measure is its high citation. The lab has always been funded by more than one NHLBI grant and for 15 years I was also the PI of a large PPG in Transfusion Biology. However, in the recent difficult funding period too much of my time was spent on securing support for my group. Obtaining prolonged funding would free my time for more mentoring, writing reviews, and collegiate activities. In addition, we now study chronic inflammatory diseases and their impact on aging. These experiments take time and the extended duration of support would assure that we could pursue this exiting research effectively.