Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, USA.
Matrix Biol. 2023 Jun;120:1-23. doi: 10.1016/j.matbio.2023.04.003. Epub 2023 Apr 20.
The extracellular matrix (ECM) is an intricate network composed of various multi-domain macromolecules like collagen, proteoglycans, and fibronectin, etc., that form a structurally stable composite, contributing to the mechanical properties of tissue. However, matricellular proteins are non-structural, secretory extracellular matrix proteins, which modulate various cellular functions via interacting with cell surface receptors, proteases, hormones, and cell-matrix. They play essential roles in maintaining tissue homeostasis by regulating cell differentiation, proliferation, adhesion, migration, and several signal transduction pathways. Matricellular proteins display a broad functionality regulated by their multiple structural domains and their ability to interact with different extracellular substrates and/or cell surface receptors. The expression of these proteins is low in adults, however, gets upregulated following injuries, inflammation, and during tumor growth. The marked elevation in the expression of these proteins during atherosclerosis suggests a positive association between their expression and atherosclerotic lesion formation. The role of matricellular proteins in atherosclerosis development has remained an area of research interest in the last two decades and studies revealed these proteins as important players in governing vascular function, remodeling, and plaque formation. Despite extensive research, many aspects of the matrix protein biology in atherosclerosis are still unknown and future studies are required to investigate whether targeting pathways stimulated by these proteins represent viable therapeutic approaches for patients with atherosclerotic vascular diseases. This review summarizes the characteristics of distinct matricellular proteins, discusses the available literature on the involvement of matrix proteins in the pathogenesis of atherosclerosis and suggests new avenues for future research.
细胞外基质 (ECM) 是一种由多种多结构域大分子组成的复杂网络，如胶原蛋白、蛋白聚糖和纤连蛋白等，它们形成结构稳定的复合物，有助于组织的机械性能。然而，基质细胞蛋白是非结构的、分泌型细胞外基质蛋白，通过与细胞表面受体、蛋白酶、激素和细胞基质相互作用，调节各种细胞功能。它们通过调节细胞分化、增殖、黏附、迁移和几种信号转导途径，在维持组织稳态方面发挥着重要作用。基质细胞蛋白通过其多个结构域及其与不同细胞外基质和/或细胞表面受体相互作用的能力，表现出广泛的功能。这些蛋白质在成年人中的表达水平较低，但在受伤、炎症和肿瘤生长期间会上调。这些蛋白质在动脉粥样硬化中的表达显著升高表明，它们的表达与动脉粥样硬化病变的形成之间存在正相关。在过去的二十年中，基质蛋白在动脉粥样硬化发展中的作用一直是研究的热点，研究表明这些蛋白是调节血管功能、重塑和斑块形成的重要参与者。尽管进行了广泛的研究，但基质蛋白生物学在动脉粥样硬化中的许多方面仍然未知，需要进一步的研究来探讨针对这些蛋白刺激的途径是否代表动脉粥样硬化血管疾病患者的可行治疗方法。本文综述了不同基质细胞蛋白的特性，讨论了基质蛋白在动脉粥样硬化发病机制中的作用的现有文献，并为未来的研究提出了新的途径。
