LncRNA-LUNAR1 Levels Are Closely Related to Coronary Collaterals in Patients with Chronic Total Coronary Occlusion

• DOI: 10.1007/s12265-019-09917-x
• Publication Date: 2020-01-29T18:02:32Z
• Authors: Wenbin Lu; Zulong Sheng; Ziwei Zhang; Genshan Ma; Lijuan Chen; Jian Huang; Jiandong Ding; Qiming Dai
• Keywords: Male; Lipopolysaccharide Receptors; Collateral Circulation; Neovascularization, Physiologic; Middle Aged; GPI-Linked Proteins; Prognosis; 03 medical and health sciences; 0302 clinical medicine; Coronary Occlusion; Coronary Circulation; Chronic Disease; Leukocytes, Mononuclear; Humans; Female; RNA, Long Noncoding; Inflammation Mediators; Cell-Free Nucleic Acids; Cells, Cultured; Chemokine CCL2; Aged; Endothelial Progenitor Cells

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, CD14++CD16- 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 CD14++CD16- 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 CD14++CD16- monocytes and CCL2, may be risk factors affecting LncRNA-LUNAR1 expression.