Wang Zhongqun, Zhang Lili, Li Lihua, Zhou Mengxue
Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People's Republic of China.
Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People's Republic of China.
Diabetes Metab Syndr Obes. 2022 Sep 28;15:3027-3038. doi: 10.2147/DMSO.S380986. eCollection 2022.
Angiogenesis is an essential promoter of atherosclerotic plaque rupture. However, the mechanism of its regulation is not understood. OTUD6B regulates cell proliferation, migration, and angiogenesis. We investigated the role of OTUD6B in angiogenesis in diabetic atherosclerotic plaques.
The expression of OTUD6B was analyzed by single cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) and evaluated by Immunofluorescence in human anterior tibial arteries from diabetic amputees and ApoE mice. Furthermore, we constructed a mouce model of diabetic atherosclerosis and used the mice to study the effect of OTUD6B downregulation in vivo by injecting them with AAV-shOTUD6B. Mouse brain microvascular endothelial cells (MBVECs) were treated with normal glucose and high lipid (NG/HL) or high glucose and high lipid (HG/HL), and siOTUD6B was used to investigate the effect of OTUD6B on proliferation, migration, and lumen formation of endothelial cells.
We found that OTUD6B expression was markedly downregulated in human anterior tibial arteries from diabetic amputees and ApoE mice. The silencing of OTUD6B resulted in diabetic atherosclerotic mice plaque instability and increased angiogenesis. In addition, the silencing of OTUD6B expression enhanced the proliferation, migration, and lumen formation of endothelial cells.
OTUD6B can reduce angiogenesis in atherosclerotic plaques, enhance plaque stability and delay the progression of atherosclerosis by regulating the proliferation, migration, and lumen formation of endothelial cells.
血管生成是动脉粥样硬化斑块破裂的重要促进因素。然而，其调控机制尚不清楚。OTUD6B调节细胞增殖、迁移和血管生成。我们研究了OTUD6B在糖尿病动脉粥样硬化斑块血管生成中的作用。
通过单细胞RNA测序（scRNA-seq）和RNA测序（RNA-seq）分析OTUD6B的表达，并通过免疫荧光在糖尿病截肢患者的人胫前动脉和载脂蛋白E（ApoE）小鼠中进行评估。此外，我们构建了糖尿病动脉粥样硬化小鼠模型，并通过向小鼠注射腺相关病毒-shOTUD6B（AAV-shOTUD6B）来研究体内下调OTUD6B的效果。用正常葡萄糖和高脂（NG/HL）或高葡萄糖和高脂（HG/HL）处理小鼠脑微血管内皮细胞（MBVECs），并使用小干扰RNA（siOTUD6B）来研究OTUD6B对内皮细胞增殖、迁移和管腔形成的影响。
我们发现糖尿病截肢患者的人胫前动脉和ApoE小鼠中OTUD6B表达明显下调。OTUD6B的沉默导致糖尿病动脉粥样硬化小鼠斑块不稳定并增加血管生成。此外，OTUD6B表达的沉默增强了内皮细胞的增殖、迁移和管腔形成。
OTUD6B可通过调节内皮细胞的增殖、迁移和管腔形成来减少动脉粥样硬化斑块中的血管生成，增强斑块稳定性并延缓动脉粥样硬化的进展。
