Abstract:
Unresolved inflammation is a key mediator of advanced heart failure. Especially, damage, pathogen, and lifestyle-associated molecular patterns are the major factors in initiating baseline inflammatory diseases, particularly in cardiac pathology. After a significant cardiac injury like a heart attack, splenic and circulating leukocytes begin a highly optimized sequence of immune cell recruitment (neutrophils and monocytes) to coordinate effective tissue repair. An injured cardiac tissue repair and homeostasis are dependent on clearance of cellular debris where the recruited leukocytes transition from a pro-inflammatory to a reparative program through resolution process. After a cardiac injury, macrophages play a decisive role in cardiac repair through the biosynthesis of endogenous lipid mediators that ensure a timely tissue repair while avoiding chronic inflammation and impaired cardiac repair. However, dysregulation of resolution of inflammation processes due to cardiometabolic defects (obesity, hypertension, and diabetes), aging, or co-medication(s) lead to impaired cardiac repair. Hence, the presented review demonstrates the fundamental role of leukocytes, in particular macrophages orchestrate the inflammation and resolution biology, focusing on the biosynthesis of specialized lipid mediators in cardiac repair and heart failure. This work was supported by research funds from National Institutes of Health (AT006704, HL132989, and HL144788) to G.V.H. The authors acknowledges the use of Servier Medical Art image bank and Biorender that is used to create schematic Figures 1-3.
摘要:
未解决的炎症是晚期心力衰竭的关键介质。尤其是,损坏,病原体,与生活方式相关的分子模式是引发基线炎症性疾病的主要因素,特别是在心脏病理学中。在像心脏病发作这样的严重心脏损伤之后,脾和循环白细胞开始高度优化的免疫细胞募集序列(中性粒细胞和单核细胞),以协调有效的组织修复。受损的心脏组织修复和体内平衡取决于细胞碎片的清除,其中募集的白细胞通过分解过程从促炎程序过渡到修复程序。心脏受伤后,巨噬细胞通过内源性脂质介质的生物合成在心脏修复中起决定性作用,确保及时的组织修复,同时避免慢性炎症和受损的心脏修复。然而,由于心脏代谢缺陷导致的炎症过程分解失调(肥胖,高血压,和糖尿病),老化,或共同用药导致心脏修复受损。因此,这篇综述证明了白细胞的基本作用,特别是巨噬细胞协调炎症和分解生物学,专注于心脏修复和心力衰竭中专门的脂质介质的生物合成。这项工作得到了美国国立卫生研究院(AT006704,HL132989和HL144788)对G.V.H的研究基金的支持。作者承认使用Servier医学艺术图像库和Biorder来创建示意图1-3。