阿斯素通过调节血管光滑肌细胞的表型转变来加剧动脉样硬化
Yu Zhao1, Zhengkai Wang2, Yi Chen2
1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China; Department of Pathophysiology, Province Key Laboratory of Medicine-Food Homologous Resources and Prevention and Treatment of Metabolic Diseases, Basic Medical College, Qiqihar Medical University, Qiqihar 161000, China.
阿斯素是一种新发现的阿迪波金,通过诱导血管光滑肌细胞 (VSMC) 现型转变来促进动脉样硬化. 向阿斯素-GPR54通路可能为动脉样硬化提供新的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 代谢疾病研究研究
- 细胞信号通道 细胞信号通道
背景情况:
- 血管光滑肌细胞 (VSMC) 现型转变是动脉样硬化发展的关键因素.
- 亚斯素是一种新型的阿迪波金,调节新陈代谢,但其在VSMC可塑性和动脉样硬化中的作用尚不清楚.
研究的目的:
- 调查阿斯素对VSMC表型转变和动脉样硬化进展的影响.
- 阐明涉及VSMC中阿斯素信号传递的潜在分子机制.
主要方法:
- 在ApoE-/-小鼠中的动脉样硬化模型.
- 使用阿斯素,阿斯素抗体和阿斯素 Knockdown (AspKD).
- 对GPR54/Gαq/11-PLC-PKC-ERK1/2-STAT3信号通路激活的研究.
主要成果:
- 升高的阿斯素水平与动脉样硬化的严重程度相关.
- 在小鼠中,阿斯素促进了VSMC表型转变,斑块形成和血管硬.
- 亚斯素诱导的效应是通过GPR54结合和随后激活Gαq/11-PLC-PKC-ERK1/2-STAT3通路进行的.
结论:
- 亚斯素通过GPR54/Gαq/11依赖ERK1/2-STAT3通路诱导VSMC表型转换而加剧动脉样硬化.
- 亚斯素-GPR54轴是治疗动脉样硬化的潜在治疗点.
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