LncRNA SLC8A1‐AS1 protects against myocardial damage through activation of cGMP‐PKG signaling pathway by inhibiting SLC8A1 in mice models of myocardial infarction

Abstract

Extensive investigations into long noncoding RNAs (lncRNAs) in various diseases and cancers, including acute myocardial infarction (AMI) have been conducted. The current study aimed to investigate the role of lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1‐AS1) in myocardial damage by targeting solute carrier family 8 member A1 (SLC8A1) via cyclic guanosine 3′,5′‐monophosphate‐protein kinase G (cGMP‐PKG) signaling pathway in AMI mouse models. Differentially expressed lncRNA in AMI were initially screened and target relationship between lncRNA SLC8A1‐AS1 and SLC8A1 was then verified. Infarct size, levels of inflammatory factors, biochemical indicators, and the positive expression of the SLC8A1 protein in AMI were subsequently determined. The expression of SLC8A1‐AS1, SLC8A1, PKG1, PKG2, atrial natriuretic peptide, and brain natriuretic peptide was detected to assess the effect of SLC8A1‐AS1 on SLC8A1 and cGMP‐PKG. The respective contents of superoxide dismutase, lactate dehydrogenase (LDH), and malondialdehyde (MDA) were detected accordingly. Microarray data GSE66360 provided evidence indicating that SLC8A1‐AS1 was poorly expressed in AMI. SLC8A1 was verified to be a target gene of lncRNA SLC8A1‐AS1. SLC8A1‐AS1 upregulation decreased levels of left ventricular end‐systolic diameter, −dp/ dt max, interleukin 1β (IL‐1β), IL‐6, transforming growth factor α, nitric oxide, inducible nitric‐oxide synthase, endothelial nitric‐oxide synthase, infarct size, LDH activity and MDA content, and increased IL‐10, left ventricular end‐diastolic pressure and + dp/ dt max. Furthermore, the overexpression of SLC8A1‐AS1 was noted to elicit an inhibitory effect on the cGMP‐PKG signaling pathway via SLC8A1. In conclusion, lncRNA SLC8A1‐AS1, by downregulating SLC8A1 and activating the cGMP‐PKG signaling pathway, was observed to alleviate myocardial damage, inhibit the release of proinflammatory factors and reduce infarct size, ultimately protecting against myocardial damage.

LINC00528 regulates myocardial infarction by targeting the miR-143-3p/COX-2 axis

“…Recently, Guo et al showed that LINC00528 was one of the most upregulated lncRNA in MI tissues compared to normal tissues [15]. Zhou et al revealed that LINC00528 was one of the most upregulated lncRNA in CHD tissues compared with normal tissues [14].…”

“…LncRNAs have been highlighted as key factors in the progression of AMI. Recently, studies showed that LINC00528 was one of the most upregulated lncRNA in coronary heart disease [14,15]. However, the roles and underlying mechanisms of LINC00528 in MI remain unclear.…”

Long noncoding RNA MALAT1 promotes cardiomyocyte apoptosis after myocardial infarction via targeting miR-144-3p

“…LncRNA AK088388 was reported to promote autophagy via direct binding of miR-30a to affect myocardial I/R injury [10]. Xu et al reported that lncRNA SLC8A1-AS1 could activate the cGMP-PKG signaling pathways to protect myocardial damage in mouse MI model [11]. Moreover, down-regulation of lncMIRT1 improved the I/R-induced injury in aged diabetic rat model though inhibition of NFκB signaling pathway [12].…”

Knockdown long noncoding RNA SLC8A1-AS1 attenuate cell invasion and migration in glioma via suppression of Wnt-β catenin signaling pathways

“…LncRNA SLC8A1-AS1 is oriented in an antisense direction to the protein-coding gene SLC8A1, which is located on chromosome 2 of the human genome [14]. SLC8 gene is a member of CaCA (Ca 2+ /Cation Antiporter) superfamily, encoding Na + /Ca 2+ exchangers (NCX), mainly expressed on cell membrane, mediate Na + /Ca 2+ uxes across the cell-membrane.…”