The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.
Pharmacol Res. 2022 May;179:106236. doi: 10.1016/j.phrs.2022.106236. Epub 2022 Apr 25.
Atherosclerosis is a chronic inflammatory disease and the pathological basis of many fatal cardiovascular diseases. Macrophages, the main inflammatory cells in atherosclerotic plaque, have a paradox role in disease progression. In response to different microenvironments, macrophages mainly have two polarized directions: pro-inflammatory macrophages and anti-inflammatory macrophages. More and more evidence shows that macrophage is mechanosensitive and matrix stiffness regulate macrophage phenotypes in atherosclerosis. However, the molecular mechanism of matrix stiffness regulating macrophage polarization still lacks in-depth research, which hinders the development of new anti-atherosclerotic therapies. In this review, we discuss the important role of matrix stiffness in regulating macrophage polarization through mechanical signal transduction (Hippo, Piezo, cytoskeleton, and integrin) and epigenetic mechanisms (miRNA, DNA methylation, and histone). We hope to provide a new perspective for atherosclerosis therapy by targeting matrix stiffness and macrophage polarization.
动脉粥样硬化是一种慢性炎症性疾病，也是许多致命心血管疾病的病理基础。巨噬细胞是动脉粥样硬化斑块中的主要炎症细胞，在疾病进展中具有矛盾的作用。巨噬细胞在响应不同的微环境时，主要有两个极化方向：促炎型巨噬细胞和抗炎型巨噬细胞。越来越多的证据表明，巨噬细胞是力学敏感的，细胞外基质硬度调节动脉粥样硬化中的巨噬细胞表型。然而，细胞外基质硬度调节巨噬细胞极化的分子机制仍缺乏深入研究，这阻碍了新的抗动脉粥样硬化治疗方法的发展。在这篇综述中，我们通过机械信号转导（Hippo、Piezo、细胞骨架和整合素）和表观遗传机制（miRNA、DNA 甲基化和组蛋白）讨论了细胞外基质硬度在调节巨噬细胞极化中的重要作用。我们希望通过靶向细胞外基质硬度和巨噬细胞极化，为动脉粥样硬化治疗提供新的视角。
