Diabetes, Metabolic Syndrome and Obesity (Sep 2022)
Loss of OTUD6B Stimulates Angiogenesis and Promotes Diabetic Atherosclerosis
Abstract
Zhongqun Wang,1,* Lili Zhang,1,* Lihua Li,2 Mengxue Zhou1 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengxue Zhou, Department of Cardiology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, 212001, People’s Republic of China, Tel +86 511 85030586, Email [email protected]: 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.Patients and Methods: 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.Results: 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.Conclusion: 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.Keywords: OTUD6B, angiogenesis, atherosclerosis, diabetes
