| First Author | Lv P | Year | 2021 |
| Journal | Oxid Med Cell Longev | Volume | 2021 |
| Pages | 5564884 | PubMed ID | 33859778 |
| Mgi Jnum | J:316072 | Mgi Id | MGI:6809089 |
| Doi | 10.1155/2021/5564884 | Citation | Lv P, et al. (2021) SM22alpha Loss Contributes to Apoptosis of Vascular Smooth Muscle Cells via Macrophage-Derived circRasGEF1B. Oxid Med Cell Longev 2021:5564884 |
| abstractText | Vascular smooth muscle cell (VSMC) apoptosis is a major defining feature of abdominal aortic aneurysm (AAA) and mainly caused by inflammatory cell infiltration. Smooth muscle (SM) 22alpha prevents AAA formation through suppressing NF-kappaB activation. However, the role of SM22alpha in VSMC apoptosis is controversial. Here, we identified that SM22alpha loss contributed to apoptosis of VSMCs via activation of macrophages. Firstly, deficiency of SM22alpha enhanced the interaction of VSMCs with macrophages. Macrophages were retained and activated by Sm22alpha (-/-) VSMCs via upregulating VCAM-1 expression. The ratio of apoptosis was increased by 1.62-fold in VSMCs treated with the conditional media (CM) from activated RAW264.7 cells, compared to that of the control CM (P < 0.01), and apoptosis of Sm22alpha (-/-) VSMCs was higher than that of WT VSMCs (P < 0.001). Next, circRasGEF1B from activated macrophages was delivered into VSMCs promoting ZFP36 expression via stabilization of ZFP36 mRNA. Importantly, circRasGEF1B, as a scaffold, guided ZFP36 to preferentially bind to and decay Bcl-2 mRNA in a sequence-specific manner and triggered apoptosis of VSMCs, especially in Sm22alpha (-/-) VSMCs. These findings reveal a novel mechanism by which the circRasGEF1B-ZFP36 axis mediates macrophage-induced VSMC apoptosis via decay of Bcl-2 mRNA, whereas Sm22alpha (-/-) VSMCs have a higher sensitivity to apoptosis. |
