Senescence dysregulates of inflammation-resolution programs in atherosclerosis

动脉粥样硬化炎症消退程序的衰老失调

• 批准号: 10333044
• 负责人: Gabrielle Fredman
• 金额: $ 4.84万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10333044
• 关键词: Administrative Supplement; Atherosclerosis; Cardiovascular Diseases; Cause of Death; Cell Aging; Cell Cycle Arrest; Cells; Chronic; Eating; Equilibrium; Goals; Industrialization; Inflammation; Inflammatory; Inflammatory Response; Learning; Leukotrienes; Lipoxins; Mediating; Mediator of activation protein; Mus; Phenotype; Process; Prostaglandins; Resolution; Signal Pathway; Signal Transduction; Techniques; Work; driving force; macrophage; novel; parent grant; prevent; programs; restoration; senescence; treatment strategy

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.

项目摘要 动脉粥样硬化性心血管疾病（CVD）是工业化国家的首要死因。 慢性炎症反应的缓解是动脉粥样硬化进展的重要驱动力。 解决是通过专门的促解决调解者（SPM）之间的关键平衡来调节的，例如 脂氧素和分解素以及白三烯 (LT) 和前列腺素 (PG) 等促炎因子。 工作 SPM 处理斑块和 b) 与保护相关的机制 因此，本行政补充的总体目标是促进 SPM 在动脉粥样硬化中的作用。 Masharh Lipscomb 了解动脉粥样硬化失调解决的新机制并 利用新的 SPM 信号通路来制定新的细胞衰老治疗策略。 不可逆的细胞周期停滞，导致高度促炎的表型，称为衰老- 以前的 我们实验室和其他人的研究表明，斑块中 SPM 的合成有缺陷，并且斑块中的 SPM 的恢复 防止小鼠动脉粥样硬化进展我们对 a) 细胞的理解仍存在差距。 扰乱 SPM 的合成 我们和其他人观察到衰老细胞在相关分泌表型（SASP）中积累。 动脉粥样硬化 已清除 Masharh 工作的一个主要目标是揭示为什么这些有害细胞不能轻易被清除 并被中和。我们假设 SASP 推动了关键的“不要吃我”信号的增加，这些信号诱导 巨噬细胞限制清除。这种行政补充将使 Masharh Lipscomb 学习新的知识。 技术，同时还提高了母基金的可交付成果的质量。