长卷环蛋白NECC2调节了oxLDL诱导的内皮氧化损伤,并加剧了无脂蛋白E小鼠的动脉样硬化发展
Xin Mu1, Shu-Jun Liu2, Lei-Yin Zheng2
1School of Biological Science and Technology, University of Jinan, Jinan, 250022, China; The Institute for Tissue Engineering and Regenerative Medicine, Liaocheng University/Liaocheng People's Hospital, Liaocheng, Shangdong, 252000, China.
Free radical biology & medicine
|March 10, 2024
概括
通过氧化低密度脂蛋白 (oxLDL) 损害血管内皮细胞 (VECs),NECC2蛋白促进动脉样硬化. 抑制NECC2可以防止VEC损伤,并减少动脉样硬化发展.
科学领域:
- 心血管生物学 心血管生物学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 氧化低密度脂蛋白 (oxLDL) 引发内皮氧化损伤,这是动脉样硬化发展的关键因素.
- 洞穴对于血管内皮细胞 (VEC) 的生存和功能至关重要,但NECC2蛋白在它们中的作用尚不清楚.
研究的目的:
- 调查NECC2在oxLDL诱导的VEC损伤和动脉样硬化中的作用.
- 阐明NECC2影响VEC功能和疾病进展的分子机制.
主要方法:
- 在小鼠主动脉和oxLDL治疗的人类脉内皮细胞 (HUVECs) 中评估了NECC2表达.
- 使用NECC2 siRNA,化合物YF-307和携带腺相关病毒 (AAV) 的NECC2 shRNA来抑制NECC2.
- 进行免疫沉以确定NECC2相互作用伙伴,并分析下游信号通路,包括Cav-1酸化,oxLDL吸收,活性氧物种 (ROS) 生成和NF-κB激活.
主要成果:
- 在动脉样硬化内皮和oxLDL治疗的HUVEC中,NECC2表达升高.
- 在apoE-/-小鼠中,NECC2抑制显著降低了oxLDL诱导的VEC亡,粘附因子表达和内皮损伤.
- NECC2与Tyk2和caveolin-1 (Cav-1) 相互作用,通过激活Tyk2来促进Tyr14中的Cav-1酸化,这会调解oxLDL诱导的VEC损伤.
结论:
- 通过Tyk2通路调节Cav-1酸化,NECC2有助于oxLDL诱导的VEC损伤和动脉样硬化.
- 准NECC2为动脉样硬化治疗提供了一个新的治疗策略.
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