依赖于lysyl氧化酶的细胞外矩阵交联调节动脉样硬化和大动脉膜疾病中的化
Carme Ballester-Servera1, Judith Alonso1, Laia Cañes1
1Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Barcelona, Spain; CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
|September 20, 2023
概括
氨酸氧化酶 (LOX) 通过改变细胞外基质的特性,促进心血管化. 抑制LOX可以减少化,这表明它是性大动脉病和动脉样硬化的治疗标.
科学领域:
- 心血管生物学 心血管生物学
- 生物化学 生物化学
- 病理学 病理学 病理学
背景情况:
- 心血管化 (CVC) 是一个严重的健康问题,治疗选择有限.
- 细胞外基质 (ECM) 在CVC中起着至关重要的作用.
- 烯酸氧化酶 (LOX) 修改了ECM的生物力学特性.
研究的目的:
- 为了研究LOX在动脉疾病 (CAVD) 和动脉样硬化中的作用.
- 为了确定LOX是否是CVC的潜在治疗点.
主要方法:
- 人类CAVD患者样本中的LOX表达分析.
- 使用膜间歇细胞 (VIC) 和骨质基的体外研究.
- 使用β-aminopropionitrile (BAPN) 的LOX的药理抑制.
- 在体内研究使用野生型 (WT) 和LOX过度表达的转基因小鼠 (TgLOXVSMC) 诱导动脉样硬化.
主要成果:
- 在化门和动脉样硬化病变中,LOX被上调,与RUNX2.2同定位.
- 在体外,LOX抑制减弱了原沉积和化.
- 在小鼠中LOX过度表达加剧了动脉样硬化负担和化.
- 洛克斯转基因增加了斑块炎症,VSMC细胞性和原交联.
结论:
- 洛克斯是心血管化的关键媒介.
- 准LOX可能为CVC提供一种新的治疗策略,包括CAVD和动脉样硬化.
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