Protective effect of SERCA2a-SUMOylation by SUMO-1 on diabetes-induced atherosclerosis and aortic vascular injury.

IF 3.5 2区 生物学 Q3 CELL BIOLOGY
Molecular and Cellular Biochemistry Pub Date : 2025-01-01 Epub Date: 2024-03-05 DOI:10.1007/s11010-024-04953-x
Jinlin Liu, Shifang Xu, Bin Gao, Meng Yuan, Li Zhong, Rui Guo
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Abstract

Diabetes is a major risk factor for cardiovascular disease. However, the exact mechanism by which diabetes contributes to vascular damage is not fully understood. The aim of this study was to investigate the role of SUMO-1 mediated SERCA2a SUMOylation in the development of atherosclerotic vascular injury associated with diabetes mellitus. ApoE-/- mice were treated with streptozotocin (STZ) injection combined with high-fat feeding to simulate diabetic atherosclerosis and vascular injury. Human aortic vascular smooth muscle cells (HAVSMCs) were treated with high glucose (HG, 33.3 mM) and palmitic acid (PA, 200 µM) for 24 h to mimic a model of diabetes-induced vascular injury in vitro. Aortic vascular function, phenotypic conversion, migration, proliferation, intracellular Ca2+ concentration, the levels of small ubiquitin-like modifier type 1 (SUMO1), SERCA2a and SUMOylated SERCA2a were detected. Diabetes-induced atherosclerotic mice presented obvious atherosclerotic plaques and vascular injury, companied by significantly lower levels of SUMO1 and SERCA2a in aorta. HG and PA treatment in HAVSMCs reduced the expressions of SUMO1, SERCA2a and SUMOylated SERCA2a, facilitated the HAVSMCs phenotypic transformation, proliferation and migration, attenuated the Ca2+ transport, and increased the resting intracellular Ca2+ concentration. We also confirmed that SUMO1 directly bound to SERCA2a in HAVSMCs. Overexpression of SUMO1 restored the function and phenotypic contractile ability of HAVSMCs by upregulating SERCA2a SUMOylation, thereby alleviating HG and PA-induced vascular injury. These observations suggest an essential role of SUMO1 to protect diabetes-induced atherosclerosis and aortic vascular injury by the regulation of SERCA2a-SUMOylation and calcium homeostasis.

Abstract Image

SUMO-1的SERCA2a-SUMO化对糖尿病诱发的动脉粥样硬化和主动脉血管损伤的保护作用
糖尿病是心血管疾病的主要风险因素。然而,糖尿病导致血管损伤的确切机制尚不完全清楚。本研究旨在探讨SUMO-1介导的SERCA2a SUMOylation在与糖尿病相关的动脉粥样硬化性血管损伤中的作用。对载脂蛋白E-/-小鼠进行链脲佐菌素(STZ)注射和高脂喂养,以模拟糖尿病动脉粥样硬化和血管损伤。用高糖(HG,33.3 mM)和棕榈酸(PA,200 µM)处理人主动脉血管平滑肌细胞(HAVSMCs)24小时,模拟糖尿病诱导的体外血管损伤模型。检测了主动脉血管功能、表型转换、迁移、增殖、细胞内 Ca2+ 浓度、小泛素样修饰物 1 型(SUMO1)、SERCA2a 和 SUMOylated SERCA2a 的水平。糖尿病诱导的动脉粥样硬化小鼠出现了明显的动脉粥样硬化斑块和血管损伤,同时主动脉中的SUMO1和SERCA2a水平显著降低。HG 和 PA 处理 HAVSMCs 可降低 SUMO1、SERCA2a 和 SUMOylated SERCA2a 的表达,促进 HAVSMCs 表型转化、增殖和迁移,减弱 Ca2+ 转运,提高静息细胞内 Ca2+ 浓度。我们还证实,SUMO1 直接与 HAVSMCs 中的 SERCA2a 结合。通过上调 SERCA2a SUMOylation,过表达 SUMO1 恢复了 HAVSMC 的功能和表型收缩能力,从而减轻了 HG 和 PA 诱导的血管损伤。这些观察结果表明,SUMO1 在通过调节 SERCA2a-SUMOylation 和钙稳态保护糖尿病诱导的动脉粥样硬化和主动脉血管损伤方面发挥着重要作用。
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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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