关键词: atherosclerosis extracellular matrix myeloperoxidase oxidation-reduction peroxynitrite post translational modification

Mesh : Humans Extracellular Matrix Proteins / metabolism Animals Oxidants / metabolism Protein Processing, Post-Translational Extracellular Matrix / metabolism

来  源:   DOI:10.1042/BST20230860

Abstract:
The extracellular matrix (ECM) is critical to biological architecture and determines cellular properties, function and activity. In many situations it is highly abundant, with collagens and elastin being some of the most abundant proteins in mammals. The ECM comprises of multiple different protein species and sugar polymers, with both different isoforms and post-translational modifications (PTMs) providing a large variety of microenvironments that play a key role in determining tissue structure and health. A number of the PTMs (e.g. cross-links) present in the ECM are critical to integrity and function, whereas others are deleterious to both ECM structure and associated cells. Modifications induced by reactive oxidants and electrophiles have been reported to accumulate in some ECM with increasing age. This accumulation can be exacerbated by disease, and in particular those associated with acute or chronic inflammation, obesity and diabetes. This is likely to be due to higher fluxes of modifying agents in these conditions. In this focused review, the role and effects of oxidants and other electrophiles on ECM are discussed, with a particular focus on the artery wall and atherosclerotic cardiovascular disease. Modifications generated on ECM components are reviewed, together with the effects of these species on cellular properties including adhesion, proliferation, migration, viability, metabolic activity, gene expression and phenotype. Increasing data indicates that ECM modifications are both prevalent in human and mammalian tissues and play an important role in disease development and progression.
摘要:
细胞外基质(ECM)对生物结构至关重要,并决定细胞特性,功能和活动。在许多情况下,它是非常丰富的,胶原蛋白和弹性蛋白是哺乳动物中最丰富的蛋白质。ECM由多种不同的蛋白质种类和糖聚合物组成,与不同的同工型和翻译后修饰(PTM)提供了各种各样的微环境,在决定组织结构和健康中起着关键作用。ECM中存在的许多PTM(例如交联)对完整性和功能至关重要,而其他对ECM结构和相关细胞都有害。据报道,随着年龄的增长,反应性氧化剂和亲电子试剂引起的修饰会在某些ECM中积累。这种积累可以因疾病而加剧,特别是那些与急性或慢性炎症相关的炎症,肥胖和糖尿病。这可能是由于在这些条件下改性剂的通量较高。在这次重点审查中,讨论了氧化剂和其他亲电体对ECM的作用和影响,特别关注动脉壁和动脉粥样硬化性心血管疾病。审查ECM组件上生成的修改,以及这些物种对细胞特性包括粘附的影响,扩散,迁移,生存能力,代谢活动,基因表达和表型。越来越多的数据表明ECM修饰在人类和哺乳动物组织中都很普遍,并且在疾病的发展和进展中起重要作用。
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