Dysregulation of LncRNAs ANRIL, MALAT1, and LINC00305 in Coronary Slow Flow Patients: Implications for Inflammation and Endothelial Dysfunction

Abstract

Coronary Slow Flow (CSF) is observed in individuals who experience delayed blood supply in the coronary arteries. Inflammation and endothelial dysfunction may play a role in the etiology and development of CSF. The current investigation aimed to compare the expression of specific long noncoding RNAs (lncRNAs) associated with endothelial dysfunction and inflammation in CSF patients. This case‒control study enrolled 72 CSF patients and 71 healthy individuals. Blood samples were collected, and serum marker levels were measured. The expression levels of lncRNAs ANRIL, MALAT1, and LINC00305 in peripheral blood mononuclear cells (PBMCs) were assessed using real-time Polymerase Chain Reaction (PCR). All statistical analyses were performed using SPSS 22, with the significance level set at P < 0.05. The study revealed that the relative expression of MALAT1 and LINC00305 was significantly lower in the CSF group (p < 0.01), whereas ANRIL was expressed at higher levels (p < 0.0001). The areas under the ROC curves (AUCs) for MALAT1, LINC00305, and ANRIL were 0.64, 0.66, and 0.75, respectively. Notably, the expression level of LINC00305 exhibited an inverse correlation with CSF incidence (OR: 0.83, p: 0.008) in contrast to that of ANRIL (OR: 1.43, p < 0.0001). Additionally, compared to those in the control group, the average BMI, WBC, RBC, Hb, LDH, LDL, FBS, and percentage of neutrophils in the CSF group were significantly greater (p< 0.05). lncRNA ANRIL is upregulated in CSF patients, whereas MALAT1 and LINC00305 are downregulated. Dysregulation of ANRIL, MALAT1, and LINC00305 may serve as diagnostic and predictive factors for CSF leakage.

Keywords: Coronary vessels; LncRNA; endothelium; inflammation; slow flow phenomenon.

Fig. 1

The expression of MALAT1, LINC00305, and ANRIL in CSF from patients was examined. (a-c) The expression of MALAT1, LINC00305, and ANRIL in PBMCs from the control and CSF groups was detected using qRT‒PCR. Delta Ct data are represented as individual values, including the means with 95% CIs. (d-f) The potential of MALAT1, LINC00305, and ANRIL as predictive tools for CSF patients was assessed through Receiver Operating Characteristic (ROC) curve analysis. The data, expressed as mean ± SD, were significantly different from those of the control group (**p < 0.01; ***p < 0.001; ****p < 0.0001). Abbreviations: CSF, coronary slow flow; PBMCs, peripheral blood mononuclear cells; ROC, receiver operating characteristic; AUC, area under the ROC curve

Fig. 2

The relationship between the expression of MALAT1 and three different grades of CSF TIMI was examined. Correlations between MALAT1 expression and the TFC of the LAD (a), the TFC of the LCX (b), and the TFC of the RCA were assessed using univariate linear regression analysis.

Fig. 3

The relationship between the expression of LINC00305 and three different grades of CSF TIMI was examined. The correlations between LINC00305 expression and the TFC of LAD (a), the TFC of LCX (b), and the TFC of RCA were assessed using univariate linear regression analysis. CSF, coronary slow flow; TIMI, thrombolysis in myocardial infarction; TFC, TIMI frame; mean TFC, mean TIMI frame count.

Fig. 4

The relationship between the expression of ANRIL and three different grades of CSF TIMI was examined. The correlations between ANRIL expression and the TFC of the LAD (a), the TFC of the LCX (b), and the TFC of the RCA were assessed using univariate linear regression analysis. TFC, TIMI frame count; TFC, mean TIMI frame count.

Fig. 5

Spearman’s correlations were used to analyze the RNA expression levels of three lncRNAs among the CSF group (a-c) and control group (d-f).