Department of Geriatrics and Geriatrics Center, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Front Endocrinol (Lausanne). 2021 Nov 10;12:748216. doi: 10.3389/fendo.2021.748216. eCollection 2021.
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and excessive accumulation of dysfunctional PVAT are hallmarks of pathogenesis after angioplasty. Recent genome-wide association studies reveal that single-nucleotide polymorphism (SNP) in MIA3 is associated with atherosclerosis-relevant VSMC phenotypes. However, the role of MIA3 in the vascular remodeling response to injury remains unknown. Here, we found that expression of MIA3 is increased in proliferative VSMCs and knockdown of MIA3 reduces VSMCs proliferation, migration, and inflammation, whereas MIA3 overexpression promoted VSMC migration and proliferation. Moreover, knockdown of MIA3 ameliorates femoral artery wire injury-induced neointimal hyperplasia and increases brown-like perivascular adipocytes. Collectively, the data suggest that MIA3 deficiency prevents neointimal formation by decreasing VSMC proliferation, migration, and inflammation and maintaining BAT-like perivascular adipocytes in PVAT during injury-induced vascular remodeling, which provide a potential therapeutic target for preventing neointimal hyperplasia in proliferative vascular diseases.
血管平滑肌细胞（VSMCs）的异常增殖和迁移以及功能失调的 PVAT 的过度积累是血管成形术后发病机制的标志。最近的全基因组关联研究表明，MIA3 中的单核苷酸多态性（SNP）与与动脉粥样硬化相关的 VSMC 表型有关。然而，MIA3 在损伤后血管重塑反应中的作用尚不清楚。在这里，我们发现 MIA3 的表达在增殖的 VSMCs 中增加，敲低 MIA3 可减少 VSMCs 的增殖、迁移和炎症，而 MIA3 的过表达则促进了 VSMC 的迁移和增殖。此外，敲低 MIA3 可减轻股动脉线损伤诱导的新生内膜增生并增加棕色样血管周脂肪细胞。总之，这些数据表明，MIA3 缺乏通过减少 VSMC 的增殖、迁移和炎症以及在损伤诱导的血管重塑过程中维持 PVAT 中的 BAT 样血管周脂肪细胞来防止新生内膜形成，为预防增殖性血管疾病中的新生内膜增生提供了一个潜在的治疗靶点。
