M2 Macrophage-Derived Exosomes Inhibit Atherosclerosis Progression by Regulating the Proliferation, Migration, and Phenotypic Transformation of Smooth Muscle Cells.

Background: Vascular smooth muscle cell (VSMC) intimal migration, proliferation, and phenotypic transformation from a contractile to a synthetic state are hallmarks of the progression of atherosclerotic plaques. This study aims to explore the effects of exosomes derived from M2 macrophages (Exo ^M2 ) on the pathological changes of VSMCs in atherosclerosis (AS).
Methods: Cell Counting Kit-8 (CCK8) and wound healing assays were used to examine the impact of Exo ^M2 on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, respectively. Western blotting was employed to analyze changes in the expression levels of contractile markers (e.g., alpha-smooth muscle actin [α-SMA]) and synthetic ones (e.g., osteopontin [OPN]) in VSMCs with or without Exo ^M2 treatment. ApoE ^-⁣/- mice on a high fat diet were utilized to observe the effects of Exo ^M2 on plaque progression and stability. Serial histopathological analysis was performed to elucidate the cellular mechanisms underlying the atheroprotective effects of Exo ^M2 .
Results: Compared with controls, Exo ^M2 significantly inhibited PDGF-BB-induced VSMC proliferation, migration, and phenotypic transformation in vitro . In ApoE ^-⁣/- mice, Exo ^M2 treatment led to a marked reduction in plaque size, necrotic core area, the CD68/α-SMA ratio, and matrix metalloproteinase 9 (MMP9) and OPN levels, while enhancing plaque stability.
Conclusions: Exo ^M2 inhibit AS progression by regulating VSMC proliferation, migration, and phenotypic transformation.
Competing Interests: The authors declare no conflict of interest.
(© 2024 The Author(s). Published by IMR Press.)