Vascular smooth muscle aging leads to diabetic complications such as cardiovascular and kidney diseases or diabetic foot. Therefore, understanding the mechanism of smooth muscle cell senescence in a high‐glucose (HG) environment is essential. The purpose of this study was to determine whether and how circRNA from human umbilical vein endothelial cell exosomes (HUVEC‐Exos) under HG conditions regulates the senescence of vascular smooth muscle cells (VSMCs). Combining circRNA array analysis and bioinformatics, we postulated that the circRNA‐0077930‐miR‐622‐Kras CeRNA network plays an important role in inducing senescence in VSMCs. CircRNA‐0077930 transmitted by HG‐HUVEs‐Exos induced senescence of VSMCs by down‐regulation of miR‐622 expression and up‐regulation of Kras, p21, p53 and p16 expression. Moreover, the lactate dehydrogenase (LDH) activity was significantly increased while anti‐oxidative stress marker (superoxide dismutase, SOD) activity was reduced in HG‐HUVEC‐Exos treatment VSMCs. Finally, HG‐HUVEC‐Exos with depleted‐circRNA‐0077930 is no longer able to induce cellular senescence in VSMCs. These findings provided a new light on the effective treatment of VSMC senescence.

中文翻译：

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高血糖刺激的血管内皮细胞外泌体的CircRNA‐0077930调节血管平滑肌细胞的衰老

血管平滑肌衰老会导致糖尿病并发症，例如心血管和肾脏疾病或糖尿病足。因此，了解高葡萄糖（HG）环境中平滑肌细胞衰老的机制至关重要。这项研究的目的是确定在HG条件下人脐静脉内皮细胞外泌体（HUVEC-Exos）的circRNA是否以及如何调节血管平滑肌细胞（VSMC）的衰老。结合circRNA阵列分析和生物信息学，我们推测circRNA-0077930-miR-622-Kras CeRNA网络在诱导VSMC衰老中起重要作用。HG-HUVEs-Exos传递的CircRNA-0077930通过下调miR-622表达和上调Kras，p21，p53和p16表达诱导VSMC衰老。此外，在HG-HUVEC-Exos处理的VSMC中，乳酸脱氢酶（LDH）活性显着增加，而抗氧化应激标记（超氧化物歧化酶，SOD）活性降低。最后，带有耗尽的circRNA-0077930的HG-HUVEC-Exos不再能够诱导VSMC中的细胞衰老。这些发现为VSMC衰老的有效治疗提供了新的思路。