Yuan Baohui, Liu He, Pan Xiaohua, Dong Xiaoliang, Qu Le-Feng, Sun Jia, Pan Li-Long
Wuxi School of Medicine and School of Food Science and Technology, Jiangnan University, Wuxi, China.
Department of Vascular and Endovascular Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.
Biochem Pharmacol. 2022 Apr;198:114947. doi: 10.1016/j.bcp.2022.114947. Epub 2022 Feb 7.
Neointima formation is characterized by the proliferation of vascular smooth muscle cells (VSMC). Although lysine-specific demethylase 1 (LSD1) has critical functions in several diseases, its role in neointima formation remains to be clarified. In this study, we aimed to explore the crucial role of LSD1 on neointima formation using a carotid artery injury model in mice. We observed that aberrant LSD1 expression was increased in human and mouse stenotic arteries and platelet-derived growth factor-BB (PDGF-BB)-treated VSMC. Furthermore, LSD1 knockdown significantly mitigated neointima formation in vivo and inhibited PDGF-BB-induced VSMC proliferation in vitro. We further uncovered that LSD1 overexpression exhibited opposite phenotypes in vivo and in vitro. Finally, LSD1 knockdown inhibited VSMC proliferation by increasing p21 expression, which is associated with LSD1 mediated di-methylated histone H3 on lysine 4 (H3K4me2) modification. Taken together, our data suggest that LSD1 may be a potential therapeutic target for the treatment of neointima formation.
新生内膜形成的特征是血管平滑肌细胞（VSMC）增殖。尽管赖氨酸特异性去甲基化酶1（LSD1）在多种疾病中具有关键作用，但其在新生内膜形成中的作用仍有待阐明。在本研究中，我们旨在利用小鼠颈动脉损伤模型探讨LSD1在新生内膜形成中的关键作用。我们观察到，在人和小鼠的狭窄动脉以及血小板衍生生长因子-BB（PDGF-BB）处理的VSMC中，异常的LSD1表达增加。此外，LSD1基因敲低显著减轻了体内新生内膜的形成，并在体外抑制了PDGF-BB诱导的VSMC增殖。我们进一步发现，LSD1过表达在体内和体外表现出相反的表型。最后，LSD1基因敲低通过增加p21表达来抑制VSMC增殖，这与LSD1介导的赖氨酸4上的二甲基化组蛋白H3（H3K4me2）修饰有关。综上所述，我们的数据表明LSD1可能是治疗新生内膜形成的潜在治疗靶点。
