CircXYLT1 suppresses oxidative stress and promotes vascular remodeling in aging mice carotid artery injury model of atherosclerosis via PTBP1

Gang Li , Donghui Li , Yajing Li , Bingqi Liu
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Abstract

Atherosclerosis and aortic aneurysms are prevalent cardiovascular diseases in the elderly, characterized by chronic inflammation and oxidative stress. This study explores the role of CircXYLT1 in regulating oxidative stress and vascular remodeling in age-related vascular diseases. RNA sequencing revealed a significant upregulation of CircXYLT1 in the vascular tissues of aged mice, highlighting its potential role in age-related vascular diseases. Using a carotid artery wire injury model, we performed adeno-associated virus (AAV)-mediated knockdown and overexpression of CircXYLT1. Key oxidative stress markers, including reactive oxygen species (ROS) and malondialdehyde (MDA), were measured. Knockdown of CircXYLT1 increased oxidative stress and reduced antioxidant protein expression (SOD, GPX), while overexpression led to decreased oxidative damage and enhanced vascular smooth muscle cell (VSMC) proliferation. Mechanistically, CircXYLT1 interacted with PTBP1, reducing its nuclear localization and modulating downstream chemokine signaling pathways. These findings suggest that CircXYLT1 plays a critical role in vascular remodeling and oxidative stress regulation, offering potential as a therapeutic target for managing cardiovascular diseases in aging populations.
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CircXYLT1通过pptbp1抑制衰老小鼠颈动脉粥样硬化损伤模型的氧化应激,促进血管重构。
动脉粥样硬化和主动脉瘤是老年人常见的心血管疾病,以慢性炎症和氧化应激为特征。本研究探讨CircXYLT1在年龄相关性血管疾病中调控氧化应激和血管重塑中的作用。RNA测序显示,CircXYLT1在老年小鼠血管组织中显著上调,突出了其在年龄相关血管疾病中的潜在作用。使用颈动脉丝损伤模型,我们进行了腺相关病毒(AAV)介导的CircXYLT1的敲低和过表达。检测主要氧化应激标志物,包括活性氧(ROS)和丙二醛(MDA)。敲低CircXYLT1可增加氧化应激,降低抗氧化蛋白(SOD、GPX)表达,而过表达可降低氧化损伤,增强血管平滑肌细胞(VSMC)增殖。在机制上,CircXYLT1与PTBP1相互作用,减少其核定位并调节下游趋化因子信号通路。这些发现表明CircXYLT1在血管重塑和氧化应激调节中起着关键作用,有可能作为治疗老年人群心血管疾病的治疗靶点。
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来源期刊
Experimental gerontology
Experimental gerontology Ageing, Biochemistry, Geriatrics and Gerontology
CiteScore
6.70
自引率
0.00%
发文量
0
审稿时长
66 days
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