Department of Cardiology, ZhongDa Hospital affiliated with Southeast University, Nanjing, China.
Division of Endocrinology, The Drum Tower Hospital, Nanjing University, Nanjing, China.
J Cardiovasc Transl Res. 2020 Apr;13(2):171-180. doi: 10.1007/s12265-019-09917-x. Epub 2020 Jan 29.
Coronary collaterals can effectively improve myocardial blood supply to the area of CTO (chronic total coronary occlusion) and can, thus, reduce infarct size. LUNAR1(leukemia-induced noncoding activator RNA-1) is a specific LncRNA regulated by Notch signaling that not only can enhance the expression of IGFR-1 but also can promote angiogenesis and cell survival. Here, we investigated the relationship between LncRNA-LUNAR1 levels in peripheral plasma and the formation of coronary collaterals. In total, 172 patients with CTO were enrolled and followed up for 12 months. Coronary collaterals were scored according to the Rentrop scoring system. Preclinical tests of tube formation were used to address the mechanisms behind the association between LncRNA-LUNAR1 and development of collaterals. Clinical data and inflammatory factors, including comorbidity, CD14CD16 monocytes, and CCL2 (chemokine motif ligand 2), were compared and analyzed. Real-time PCR was used to detect the expression of LncRNA-LUNAR1 in peripheral blood plasma. The Rentrop score was positively correlated with LncRNA-LUNAR1 levels in patients with CTO (R = 0.47, p < 0.001). Tube formation assay proved the direct association between LncRNA-LUNAR1 and development of collaterals (p = 0.011). The univariate Kaplan-Meier analysis revealed that patients with low LncRNA-LUNAR1 expression exhibited worse clinical outcomes than those with high LncRNA-LUNAR1 levels (p = 0.008). Receiver operating characteristic (ROC) curve and correlation analysis further confirmed that LncRNA-LUNAR1 expression was closely related to chronic inflammatory diseases, especially diabetes (area = 0.644, p = 0.001; 95% CI, 0.562-0.726). Furthermore, both CD14CD16 monocytes (r = - 0.37; p < 0.001) and CCL2 levels (r = - 0.35; p < 0.001) negatively affected the expression of LncRNA-LUNAR1. LncRNA-LUNAR1 expression was positively correlated with coronary collaterals in patients with CTO. Inflammatory factors, including CD14CD16 monocytes and CCL2, may be risk factors affecting LncRNA-LUNAR1 expression.
冠状动脉侧支可以有效地改善 CTO（慢性完全闭塞）区域的心肌血液供应，从而减少梗死面积。LUNAR1（白血病诱导的非编码激活 RNA-1）是一种受 Notch 信号调控的特异性 LncRNA，不仅可以增强 IGFR-1 的表达，还可以促进血管生成和细胞存活。在这里，我们研究了外周血浆中 LncRNA-LUNAR1 水平与冠状动脉侧支形成之间的关系。共纳入 172 例 CTO 患者，随访 12 个月。根据 Rentrop 评分系统对冠状动脉侧支进行评分。管腔形成的临床前测试用于解决 LncRNA-LUNAR1 与侧支形成之间关联的机制。比较和分析临床数据和炎症因子，包括合并症、CD14CD16 单核细胞和 CCL2（趋化因子基序配体 2）。实时 PCR 用于检测外周血血浆中 LncRNA-LUNAR1 的表达。Rentrop 评分与 CTO 患者的 LncRNA-LUNAR1 水平呈正相关（R=0.47，p<0.001）。管腔形成试验证明了 LncRNA-LUNAR1 与侧支形成之间的直接关联（p=0.011）。单变量 Kaplan-Meier 分析显示，低 LncRNA-LUNAR1 表达的患者临床结局较 LncRNA-LUNAR1 水平高的患者差（p=0.008）。接收者操作特征（ROC）曲线和相关性分析进一步证实，LncRNA-LUNAR1 表达与慢性炎症性疾病密切相关，尤其是糖尿病（面积=0.644，p=0.001；95%CI，0.562-0.726）。此外，CD14CD16 单核细胞（r=-0.37；p<0.001）和 CCL2 水平（r=-0.35；p<0.001）均负性影响 LncRNA-LUNAR1 的表达。LncRNA-LUNAR1 表达与 CTO 患者的冠状动脉侧支呈正相关。炎症因子，包括 CD14CD16 单核细胞和 CCL2，可能是影响 LncRNA-LUNAR1 表达的危险因素。
