Relation of circulating lncRNA GAS5 and miR-21 with biochemical indexes, stenosis severity, and inflammatory cytokines in coronary heart disease patients

Abstract

Background: Long noncoding RNA GAS5 (lnc-GAS5) and its target microRNA-21 (miR-21) regulate blood lipid, macrophages, Th cells, vascular smooth muscle cells to participate in atherosclerosis, and related coronary heart disease (CHD). The study aimed to further explore the linkage of their circulating expressions with common biochemical indexes, stenosis severity and inflammatory cytokines in CHD patients.

Methods: Ninety-eight CHD patients and 100 controls confirmed by coronary angiography were enrolled. Plasma samples were collected for lnc-GAS5 and miR-21 detection by reverse transcription-quantitative polymerase chain reaction and inflammatory cytokines determination by enzyme-linked immunosorbent assay.

Results: Lnc-GAS5 was increased in CHD patients compared with controls (2.270 (interquartile range [IQR]: 1.676-3.389) vs. 0.999 ([IQR: 0.602-1.409], p < 0.001), whereas miR-21 showed opposite tread (0.442 [IQR: 0.318-0.698] vs. 0.997 [IQR: 0.774-1.368], p < 0.001). In aspect of their intercorrelation, lnc-GAS5 negatively linked with miR-21 in CHD patients (p < 0.001) instead of controls (p = 0.211). Interestingly, among the common biochemical indexes, lnc-GAS5 related to decreased high-density lipoprotein cholesterol (p = 0.008) and increased C-reactive protein (CRP) (p < 0.001), while miR-21 correlated with lower total cholesterol (p = 0.024) and CRP (p < 0.001) in CHD patients. As stenosis degree, lnc-GAS5 positively correlated with Gensini score (p < 0.001), but miR-21 exhibited negative association (p = 0.003) in CHD patients. In terms of inflammatory cytokines, lnc-GAS5 positively related to tumor necrosis factor α (TNF-α) and interleukin (IL)-17A, while miR-21 negatively linked with TNF-α, IL-1β, IL-6, and IL-17 in CHD patients (all p < 0.05).

Conclusion: Circulating lnc-GAS5 and its target miR-21 exhibit potency to serve as biomarkers for CHD management.

Keywords: coronary heart disease; inflammation; lncrna GAS5; microRNA-21; stenosis severity.

FIGURE 1

Lnc‐GAS5 and miR‐21 expression. Comparison of lnc‐GAS5 expression in CHD patients compared to controls (A); discrimination of CHD patients from controls by lnc‐GAS5 (B); comparison of miR‐21 expression in CHD patients compared to controls (C); discrimination of CHD patients from controls by miR‐21 (D). AUC, area under curves; CHD, coronary heart disease; CI, confidential interval; Lnc‐GAS5, long noncoding RNA growth arrest‐specific 5; miR‐21, microRNA‐21

FIGURE 2

Association of lnc‐GAS5 with miR‐21. The correlation of lnc‐GAS5 expression with miR‐21 expression in controls (A) and CHD patients (B). CHD, coronary heart disease; Lnc‐GAS5, long noncoding RNA growth arrest‐specific 5; miR‐21, microRNA‐21

FIGURE 3

Association of lnc‐GAS5 and miR‐21 with Gensini score. The correlation of lnc‐GAS5 (A) and miR‐21 (B) expressions with Gensini score in CHD patients. CHD, coronary heart disease; Lnc‐GAS5, long noncoding RNA growth arrest‐specific 5; miR‐21, microRNA 21

FIGURE 4

Association of lnc‐GAS5 and miR‐21 with inflammation. The correlation of lnc‐GAS5 expression with inflammatory cytokines such as TNF‐α (A), IL‐1β (B), IL‐6 (C), and IL‐17 (D) levels in CHD patients; the correlation of miR‐21 expression with inflammatory cytokines such as TNF‐α (E), IL‐1β (F), IL‐6 (G), and IL‐17 (H) in CHD patients. CHD, coronary heart disease; Lnc‐GAS5, long noncoding RNA growth arrest‐specific 5; miR‐21, microRNA‐21; IL‐1β, interleukin 1β; IL‐6, interleukin 6; IL‐17, interleukin 17; TNF‐α, tumor necrosis factor α