Senescence dysregulates of inflammation-resolution programs in atherosclerosis

项目摘要 动脉粥样硬化性心血管疾病(CVD)是工业化世界的主要死亡原因。失败 慢性炎症反应的解决是动脉粥样硬化进展的重要推动力。 解决是由专门的支持解决问题的调解人(SPM)之间的关键平衡来调节的，例如 脂素和解毒剂以及促炎因子，如白三烯(LTS)和前列腺素(PGs)。 工作 SPM 处理斑块和b)与保护性 SPM在动脉粥样硬化中的作用。因此，这一行政副刊的总体目标是 Masharh Lipscomb了解动脉粥样硬化中调节失调的新机制并 利用新的SPM信号通路走向新的治疗策略。细胞衰老是一种 不可逆转的细胞周期停滞导致一种称为衰老的高度促炎表型- 上一首 来自我们实验室和其他人的研究表明，SPM是在斑块中有缺陷地合成的，而且 防止小鼠动脉粥样硬化的进展。关于a)什么细胞，我们的理解中仍然存在差距 异构化合成SPM的研究 相关分泌表型(SASP)。我们和其他人观察到衰老细胞在 动脉硬化 已清除 Masharh工作的一个主要目标是找出为什么这些有害细胞不容易 我们假设SASP推动了关键信号的增加，这些信号会诱使 巨噬细胞限制清除。这一行政副刊将允许Masharh Lipscomb学习新的 技术，同时也提高了母公司赠款交付成果的质量。

Project abstract Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the industrialized world. Failed resolution of a chronic inflammatory response is an important driving force in the progression of atherosclerosis. Resolution is mediated by the critical balance between specialized pro-resolving mediators (SPMs) such as lipoxins and resolvins and pro-inflammatory factors like leukotrienes (LTs) and prostaglandins (PGs). work SPMs processes plaques and b) mechanisms associated with the protective actions of SPMs in atherosclerosis. Therefore, the overall objective of this administrative supplement is for Masharh Lipscomb to understand new mechanisms of dysregulated resolution in atherosclerosis and to harness new SPM signaling pathways towards a novel treatment strategy. Cellular senescence is an irreversible cell cycle arrest that leads to a highly pro-inflammatory phenotype called the senescence- Previous from our lab and others suggest that SPMs are defectively synthesized in plaques and that restoration of prevents atherosclerosis progression in mice. Gaps remain in our understanding as to a) what cellular derange the synthesis of SPMs in associated secretory phenotype (SASP). We and other observed that senescent cells accumulate in atherosclerosis cleared and a major goal of Masharh work is to uncover why these harmful cells cannot be readily and neutralized.We postulate that the SASP drives an increase in key “don't' eat me” signals that coax macrophages to limit clearance. This administrative supplement will allow Masharh Lipscomb to learn new techniques while also increasing the quality of the deliverables on the parent grant.