Matrix stiffness regulates macrophage polarization in atherosclerosis

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.