The small leucine-rich repeat proteoglycans in tissue repair and atherosclerosis.
The small leucine-rich repeat proteoglycans in tissue repair and atherosclerosis.
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DOI：
10.1111/joim.12400
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发表时间：
2015-11
影响因子：
11.1
通讯作者：
Chakravarti S
中科院分区：
文献类型：
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作者：
Hultgårdh-Nilsson A;Borén J;Chakravarti S
蛋白聚糖由具有一个或多个共价连接的糖胺聚糖（GAG）侧链的蛋白质核心组成，并且在动脉粥样硬化的起始和进展中具有多种作用。在这里，我们讨论了一组富含亮氨酸的小重复蛋白聚糖（SLRP）在动脉粥样硬化中的潜在和已知功能。我们专注于5 SLRP，核心蛋白聚糖，双糖链光蛋白聚糖，纤维调节蛋白，和PRELP，因为这些已被检测到动脉粥样硬化斑块或证明有一个作用的动物模型动脉粥样硬化。核心蛋白聚糖和双糖链蛋白聚糖通过用软骨素/硫酸皮肤素GAG取代而进行后修饰，而光蛋白聚糖、纤调蛋白和PRELP具有硫酸角质素侧链，并且核心蛋白具有富含亮氨酸的重复（LRR）基序，这是LRR超家族的特征。软骨素/硫酸皮肤素GAG侧链与动脉粥样硬化中的脂质潴留有关。核心蛋白在这里讨论的背景下：（i）与胶原蛋白的相互作用及其在组织完整性，纤维化和伤口修复的影响;和（ii）与生长因子、细胞因子、病原体相关分子模式和细胞表面受体的相互作用，所述相互作用影响正常生理学和疾病过程，例如炎症，先天免疫应答，和伤口愈合（即在斑块发展和进展中都很重要的过程）。因此，在伤口愈合的背景下，这些SLRP的研究提供了有关其功能的线索，这可能是重要的动脉粥样硬化斑块的脆弱性和心血管疾病的早期阶段，在后期阶段。了解由核心蛋白相互作用调节的信号转导途径，导致这些蛋白在创伤修复和动脉粥样硬化中的新作用和治疗潜力。
Proteoglycans consist of a protein core with one or more covalently attached glycosaminoglycan (GAG) side chains, and have multiple roles in the initiation and progression of atherosclerosis. Here we discuss the potential and known functions of a group of small leucine-rich repeat proteoglycans (SLRPs) in atherosclerosis. We focus on five SLRPs, decorin, biglycan lumican, fibromodulin, and PRELP, because these have been detected in atherosclerotic plaques or demonstrated to have a role in animal models of atherosclerosis. Decorin and biglycan are modified post translationally by substitution with chondroitin/dermatan sulfate GAGs, whereas lumican, fibromodulin, and PRELP have keratan sulfate side chains, and the core proteins have leucine-rich repeat (LRR) motifs that are characteristic of the LRR superfamily. The chondroitin/dermatan sulfate GAG side chains have been implicated in lipid retention in atherosclerosis. The core proteins are discussed here in the context of: (i) interactions with collagens and their implications in tissue integrity, fibrosis, and wound repair; and (ii) interactions with growth factors, cytokines, pathogen-associated molecular patterns, and cell surface receptors that impact normal physiology and disease processes such as inflammation, innate immune responses, and wound healing (i.e processes that are all important in plaque development and progression). Thus, studies of these SLRPs in the context of wound healing are providing clues about their functions that may be important in early stages of atherosclerosis to plaque vulnerability and cardiovascular disease at later stages. Understanding of signal transduction pathways regulated by the core protein interactions is leading to novel roles and therapeutic potential for these proteins in wound repair and atherosclerosis.