| First Author | Gao L | Year | 2019 |
| Journal | Atherosclerosis | Volume | 291 |
| Pages | 78-86 | PubMed ID | 31704554 |
| Mgi Jnum | J:293524 | Mgi Id | MGI:6452874 |
| Doi | 10.1016/j.atherosclerosis.2019.10.003 | Citation | Gao L, et al. (2019) MicroRNA-21 deficiency attenuated atherogenesis and decreased macrophage infiltration by targeting Dusp-8. Atherosclerosis 291:78-86 |
| abstractText | BACKGROUND AND AIMS: Atherosclerosis is a chronic inflammatory disorder mediated by macrophage activation. MicroRNA-21 (miR-21) is a key regulator in the macrophage inflammatory response. However, the functional role of miR-21 in atherogenesis is far from clear. METHODS AND RESULTS: Here, we report that miR-21 is significantly upregulated in mouse atherosclerotic plaques and peripheral monocytes from patients with coronary artery disease. Compared with miR-21(+/+)apoE(-/-) mice (apoE(-/-) mice), miR-21(-/-)apoE(-/-) (double knockout, DKO) mice showed less atherosclerotic lesions, reduced presence of macrophages, decreased smooth muscle cells(SMC) and collagen content in the aorta. We further explored the role of miR-21 in macrophage activation in vitro. Bone marrow-derived macrophages (BMDMs) from DKO mice not only exhibit impaired function of migration induced by chemokine (C-C motif) ligand 2 (CCL2) but also a weakened macrophage-endothelium interaction activated by tumor necrosis factor-alpha (TNF-alpha). However, atherogenic inflammatory cytokine secretion was not affected by miR-21 in vitro or in vivo. Additionally, miR-21 knockdown in BMDMs directly derepressed the expression of dual specificity protein phosphatase 8 (Dusp-8), a previously validated miR-21 target in cardiac fibroblasts, which negatively regulates mitogen-activated protein kinase (MAPK) signaling, particularly the p38-and c-Jun N-terminal kinase (JNK)-related signaling pathways. CONCLUSIONS: These data demonstrate that inhibition of miR-21 may restrict the formation of atherosclerotic plaques partly by regulating macrophage migration and adhesion, while, reduced SMCs and collagen content in plaques may lead to a less stable phenotype with the progression of atherosclerosis. Thus, the absence of miR-21 reduces atherosclerotic lesions but may not represent all benefit in atherosclerosis development. |
