Abstract
This study aimed to detect the expression of the long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) and evaluate its correlation with disease risk, stenosis degree, inflammation, as well as overall survival (OS) in coronary artery disease (CAD) patients. A total of 230 patients who underwent diagnostic coronary angiography were consecutively recruited and assigned to CAD group (n=125) or control group (n=105) according to presence or absence of CAD. Gensini score was calculated to assess the severity of coronary artery damage. Plasma samples were collected and the expression ANRIL was detected in all participants. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-17 in CAD patients were measured and OS was calculated. The relative expression of ANRIL was higher in CAD patients compared to controls (P<0.001). Receiver operating characteristic disclosed that ANRIL could distinguish CAD patients from controls with an area under the curve of 0.789 (95%CI: 0.731–0.847). Spearman's rank correlation test revealed that expression of ANRIL was positively correlated with Gensini score (P=0.001), levels of hs-CRP (P=0.001), ESR (P=0.038), TNF-α (P=0.004), and IL-6 (P<0.001), while negatively correlated with IL-10 level (P=0.008) in CAD patients. Kaplan-Meier curve revealed that high expression of ANRIL was associated with shorter OS (P=0.013). In conclusion, circulating ANRIL presented a good diagnostic value for CAD, and its high expression was associated with increased stenosis degree, raised inflammation, and poor OS in CAD patients.
Highlights
Cardiovascular disease (CVD) is the leading cause of death worldwide for the last 15 years, resulting in approximately 15 million deaths according to the World Health Organization 2015 statistical report, causing a huge social economic burden [1]
Limited studies investigate the association of long non-coding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) expression with disease conditions and inflammatory responses in coronary artery disease (CAD) patients
CAD was defined as the presence of X50% of luminal stenosis in at least one major coronary vessel according to the coronary angiography, which was determined by the agreement of two independent and experienced interventional cardiologists
Summary
Cardiovascular disease (CVD) is the leading cause of death worldwide for the last 15 years, resulting in approximately 15 million deaths according to the World Health Organization 2015 statistical report, causing a huge social economic burden [1]. Additional and accurate biomarkers should be explored for predicting CAD risk and monitoring disease severity to promote early diagnosis and good prognosis in CAD patients. The lncRNA antisense noncoding RNA in the INK4 locus (ANRIL), known as cyclin-dependent kinase inhibitor 2B antisense RNA (CDKN2BAS), is located on the 9p21.3 locus and involved in the process of development and progression of many chronic diseases including CVD, intracranial aneurysm, and periodontitis [8,9]. Limited studies investigate the association of lncRNA ANRIL expression with disease conditions and inflammatory responses in CAD patients. The purpose of this study was to detect the lncRNA ANRIL expression and evaluate its correlation with disease risk, stenosis degree, inflammation, as well as overall survival (OS) in CAD patients
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