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

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Abstract

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.

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Abbreviations

CTO :

chronic total coronary occlusion

LUNAR1 :

leukemia-induced noncoding activator RNA-1

LncRNA :

long-chain noncoding RNA

IGFR-1 :

insulin-like growth factor receptor-1

CCL2 :

chemokine motif ligand 2

EPCs :

endothelial progenitor cells

MALAT1 :

metastasis-associated lung adenocarcinoma transcript 1

MEG3 :

maternally expressed 3

HOTAIR :

HOX transcript antisense RNA

eGFR :

estimated glomerular filtration rate

CTP :

Child–Turcotte–Pugh

PCI :

percutaneous coronary intervention

TIMI :

thrombolysis in myocardial infarction

hs-CRP :

hypersensitive C-reactive protein

BNP :

brain natriuretic peptide

GAPDH :

glyceraldehyde-3-phosphate dehydrogenase

LDL :

low-density lipoprotein

LvEF :

left ventricular ejection fraction

T2DM :

diabetes mellitus type 2

ROC :

receiver operating characteristic curve

CAD :

coronary artery disease

MI :

myocardial infarction

MACEs :

major adverse cardiovascular events

STAT :

signal transducers and activators of transcription

STEMI :

ST elevation myocardial infarction

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Funding

This study was financially supported by the Science and Technology Project of Nanjing (No. 201803076), the National Natural Science Foundation of China (81670326), and the Youth Medical Talents Project of Jiangsu Province (No. QNRC2016814).

Author information

Authors and Affiliations

  1. Department of Cardiology, ZhongDa Hospital affiliated with Southeast University, Nanjing, China

    Wenbin Lu, Zulong Sheng, Genshan Ma, Lijuan Chen & Jiandong Ding

  2. Division of Endocrinology, The Drum Tower Hospital, Nanjing University, Nanjing, China

    Ziwei Zhang

  3. Department of Cardiology, Lishui Branch, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China

    Jian Huang & Qiming Dai

Authors
  1. Wenbin Lu
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  2. Zulong Sheng
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  3. Ziwei Zhang
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  4. Genshan Ma
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  5. Lijuan Chen
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  6. Jian Huang
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  7. Jiandong Ding
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  8. Qiming Dai
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Contributions

Conceived and designed the experiments: Wenbin Lu and Qiming Dai. Performed the experiments: Ziwei Zhang, Jian Huang, Zulong Sheng, and Lijuan Chen. Analyzed the data and wrote the paper: Zulong Sheng, Ziwei Zhang, and Wenbin Lu. Contributed reagents/materials/analysis tools: Jiandong Ding and Genshan Ma. All the authors listed have approved the manuscript that is enclosed.

Corresponding authors

Correspondence to Wenbin Lu, Jiandong Ding or Qiming Dai.

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Ethics Approval and Consent to Participate

This program was approved by the Ethical Committee of ZhongDa Hospital affiliated with Southeast University, China. All participants provided written informed consent.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Associate Editor Craig M. Stolen oversaw the review of this article

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Lu, W., Sheng, Z., Zhang, Z. et al. LncRNA-LUNAR1 Levels Are Closely Related to Coronary Collaterals in Patients with Chronic Total Coronary Occlusion. J. of Cardiovasc. Trans. Res. 13, 171–180 (2020). https://doi.org/10.1007/s12265-019-09917-x

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  • DOI: https://doi.org/10.1007/s12265-019-09917-x

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