在牛皮和其他炎症性疾病中增加LL37促进LDL吸收和动脉样硬化
Yoshiyuki Nakamura1, Nikhil N Kulkarni1, Toshiya Takahashi1
1Department of Dermatology and.
The Journal of clinical investigation
|January 9, 2024
概括
人类抗微生物LL37增强了巨细胞的LDL吸收,这可能解释了皮病等慢性炎症疾病中心血管疾病风险增加的原因. 这种相互作用促进胆固醇的积累,有助于动脉样硬化发展.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
背景情况:
- 慢性炎症性疾病,如牛皮,与心血管疾病 (CVD) 风险增加有关.
- 在这些患者中观察到cathelicidin宿主防御LL37的水平升高.
- LL37既具有抗菌性,也具有抗炎性.
研究的目的:
- 通过研究LL37对脂蛋白代谢的影响,研究LL37在心血管疾病风险中的作用.
- 为了确定LL37是否会影响巨细胞中低密度脂蛋白 (LDL) 的吸收.
主要方法:
- 评估LL37对巨细胞LDL吸收的影响是使用LDL受体 (LDLR),食尸受体类B成员1 (SR-B1) 和CD36.
- 结构功能分析和同步机小角度X射线散射被用来研究LL37-LDL复合体.
- 使用表达LL37的Apoe-/-小鼠来评估动脉瘤斑块的发展.
- 血LL37和氧化脂在阿波利波蛋白B (OxPL-apoB) 的水平与心血管疾病患者相关.
主要成果:
- 通过LDLR,SR-B1和CD36,LL37显著增强了巨细胞中LDL的吸收.
- 这种相互作用增加了细胞质胆固醇,并改变了巨细胞中的脂质代谢基因表达.
- 结构分析确定了负责受体结合和吸收的LL37-LDL复合物的决定因素.
- 在Apoe-/-小鼠中,LL37表达导致了与对照组相比较大的动脉瘤斑块.
- 在心血管疾病患者的血LL37和OxPL-apoB水平之间发现了正相关性.
结论:
- LL37与LDL的相互作用增强了巨细胞的吸收,导致胆固醇积累增加.
- 这种机制为与慢性炎症疾病相关的心血管疾病风险增加提供了潜在的解释.
- 这些发现强调LL37作为动脉样硬化病原体的新型因素.
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