Objective

Coronary heart disease (CHD) is a notable contributor to the burden of human health. Dysregulated long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of CHD. This study investigated the expression pattern of lncRNA LOXL1-AS1 in CHD and its regulatory mechanism in oxidized low-density lipoprotein (ox-LDL)-induced human coronary artery endothelial cell (HCAEC) pyroptosis.

Methods

Serum was collected from 62 CHD patients and 62 healthy volunteers for the detection of LOXL1-AS1 expression. The value of LOXL1-AS1 in CHD diagnosis and major cardiovascular adverse event (MACE) prediction was analyzed using the ROC curve. LOXL1-AS1, miR-16-5p, and SNX16 expressions in ox-LDL-treated HCAECs were determined using RT-qPCR. NLPR3, cleaved-caspase-1, and GSDMD-N protein levels were measured using Western blot. IL-1β and IL-18 concentrations were measured using ELISA. The binding relationships between LOXL1-AS1 and miR-16-5p and miR-16-5p and SNX16 were verified. Functional rescue experiment was performed to verify the role of miR-16-5p in HCAEC pyroptosis.

Results

LOXL1-AS1 was highly expressed in CHD patients. LOXL1-AS1 had diagnostic value for CHD and predictive value for MACE occurrence. ox-LDL-treated HCAECs showed reduced viability, increased IL-1β and IL-18 concentrations, and elevated NLPR3, cleaved-caspase-1, and GSDMD-N levels. LOXL1-AS1 silencing promoted cell viability and reduced pyroptosis. LOXL1-AS1 bound to miR-16-5p and miR-16-5p targeted SNX16. Inhibition of miR-16-5p reversed the inhibitory effect of LOXL1-AS1 silencing on HCAEC pyroptosis.

Conclusion

LOXL1-AS1 was elevated in CHD patients with a good diagnostic value for CHD and predictive value for MACE. LOXL1-AS1 downregulated miR-16-5p expression by binding to miR-16-5p to enhance ox-LDL-induced HCAEC pyroptosis, which may be associated with upregulation of SNX16 transcription.

中文翻译：

---

LOXL1-AS1在冠心病中的差异表达及其在ox-LDL诱导的人冠状动脉内皮细胞焦亡中的调控机制

客观的

冠心病 (CHD) 是人类健康负担的一个显着贡献者。失调的长链非编码 RNA (lncRNA) 与冠心病的发病机制有关。本研究探讨 lncRNA LOXL1-AS1 在先心病中的表达模式及其在氧化低密度脂蛋白 (ox-LDL) 诱导的人冠状动脉内皮细胞 (HCAEC) 细胞焦亡中的调控机制。

方法

采集62名冠心病患者和62名健康志愿者的血清，检测LOXL1-AS1的表达。使用ROC曲线分析LOXL1-AS1在冠心病诊断和主要心血管不良事件（MACE）预测中的价值。使用 RT-qPCR 确定 ox-LDL 处理的 HCAEC 中的 LOXL1-AS1、miR-16-5p 和 SNX16 表达。使用蛋白质印迹测量 NLPR3、cleaved-caspase-1 和 GSDMD-N 蛋白水平。使用 ELISA 测量 IL-1β 和 IL-18 浓度。验证了 LOXL1-AS1 和 miR-16-5p 以及 miR-16-5p 和 SNX16 之间的结合关系。进行功能性挽救实验以验证 miR-16-5p 在 HCAEC 细胞焦亡中的作用。

结果

LOXL1-AS1 在冠心病患者中高表达。LOXL1-AS1对冠心病有诊断价值，对MACE发生有预测价值。ox-LDL 处理的 HCAEC 显示活力降低，IL-1β 和 IL-18 浓度升高，NLPR3、cleaved-caspase-1 和 GSDMD-N 水平升高。LOXL1-AS1 沉默促进细胞活力并减少细胞焦亡。LOXL1-AS1 与 miR-16-5p 结合，miR-16-5p 靶向 SNX16。抑制 miR-16-5p 可逆转 LOXL1-AS1 沉默对 HCAEC 细胞焦亡的抑制作用。

结论

LOXL1-AS1 在冠心病患者中升高，具有良好的冠心病诊断价值和 MACE 预测价值。LOXL1-AS1 通过与 miR-16-5p 结合来下调 miR-16-5p 表达以增强 ox-LDL 诱导的 HCAEC 细胞焦亡，这可能与 SNX16 转录上调有关。