Silencing of ATP2B1‐AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA‐mediated NF‐κB signalling pathway

Abstract

Myocardial infarction (MI) is an acute coronary syndrome that refers to tissue infarction of the myocardium. This study aimed to investigate the effect of long intergenic non-protein-coding RNA (lincRNA) ATPase plasma membrane Ca 2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) against MI by targeting nuclear factor-kappa-B inhibitor alpha (NFKBIA) and mediating the nuclear factor-kappa-B (NF-κB) signalling pathway. An MI mouse model was established and identified by cardiac function evaluation. It was determined that ATP2B1-AS1 was highly expressed, while NFKBIA was poorly expressed and NF-κB signalling pathway was activated in MI mice. Cardiomyocytes were extracted from mice and introduced with a series of mouse ATP2B1-AS1 vector, NFKBIA vector, siRNA-mouse ATP2B1-AS1 and siRNA-NFKBIA. The expression of NF-κBp50, NF-κBp65 and IKKβ was determined to identify whether ATP2B1-AS1 and NFKBIA affect the NF-κB signalling pathway, the results of which suggested that ATP2B1-AS1 down-regulated the expression of NFKBIA and activated the NF-κB signalling pathway in MI mice. Based on the data from assessment of cell viability, cell cycle, apoptosis and levels of inflammatory cytokines, either silencing of mouse ATP2B1-AS1 or overexpression of NFKBIA was suggested to result in reduced cardiomyocyte apoptosis and expression of inflammatory cytokines, as well as enhanced cardiomyocyte viability. Our study provided evidence that mouse ATP2B1-AS1 silencing may have the potency to protect against MI in mice through inhibiting cardiomyocyte apoptosis and inflammation, highlighting a great promise as a novel therapeutic target for MI. K E Y W O R D Smouse ATPase plasma membrane Ca 2+ transporting 1 antisense RNA 1, myocardial infarction, NF-kappa-B inhibitor alpha, nuclear factor-kappa-B signalling pathway | INTRODUC TI ONMyocardial infarction (MI) is a major public health concern that is commonly known as a heart attack characterized by a decline or complete stop of blood flow to the heart. 1 Since 1998, age-standardized AMI incidence decreased from 323 to 210 per 100 000 in 2007 in female and from 620 to 380 per 100 000 in 2007 in male, but socio-economic inequalities still exist in AMI incidence and have not narrowed. 2 In America, more than one million patients are | 4467 SONG et al.hospitalized due to MI annually, and the rates of readmission are approximately 20% within 30 days after discharge. 3 Moreover, the incidence of MI is increasing in China, and 23 million patients are estimated to experience MI by the end of 2030. 4 The risk factors of MI include hypertension, hypercholesterolaemia, diabetes, smoking habit, obesity, a sedentary lifestyle, excessive alcohol intake and unhealthy diet. 5,6 Earlier recognition or diagnosis of MI symptoms and prompt care-seeking actions are of great significance for the selection of the most appropriate treatments. 7 Although great improvements have been achieved in the prevention and therapies of MI, the difficulties in the prevention of MI are still steadily increasing. 8 Thus, further ef...

ATP2B1-AS1 Promotes Cerebral Ischemia/Reperfusion Injury Through Regulating the miR-330-5p/TLR4-MyD88-NF-κB Signaling Pathway

“…The potential neuroprotective effect of ATP2B1-AS1 on the cerebral I/R injury in MCAO/IR rats and OGD/R PC12 cells were explored in our study. As reported in a previous study, ATP2B1-AS1 was highly expressed in mice with myocardial infarction, while silencing of mouse ATP2B1-AS1 reduced cardiomyocyte apoptosis and inhibited the expression of inflammatory cytokines, as well as promoted the cardiomyocyte viability (Song et al, 2020). In this study, we confirmed that the expression of ATP2B1-AS1 was upregulated in a MCAO/IR rat model and OGD/R PC12 cells with a time independent manner.…”

Knockdown of circ_0060745 alleviates acute myocardial infarction by suppressing NF‐κB activation

“…The silencing of IRAK3 inactivated the NF-κB signalling pathway, thereby attenuating the progression of AMI in mice 11. The silencing of ATP2B1-AS1 had a protective effect post-MI by blocking the NF-κB pathway 30. In our study, knockdown of circ_0060745 suppressed the expressions of IL-6, IL-12, IL-1β, TNF-α and NF-κBp65 under hypoxia.…”

Transport Stress Induces Skin Innate Immunity Response in Hybrid Yellow Catfish (Tachysurus fulvidraco♀ × P. vachellii♂) Through TLR/NLR Signaling Pathways and Regulation of Mucus Secretion

“…The protein encoded by nfkbia was identified as a target for glucocorticoid-mediated immunosuppression (54). In mice, nfkbia was poorly expressed and the NF-kB signaling pathway was activated during myocardial infarction, while overexpression of nfkbia reduced the expression of inflammatory cytokines and cardiomyocyte apoptosis, and improved cardiomyocyte viability (55). Because map3k7cl was downregulated in Chinese patients with non-small cell lung cancer, Niu et al speculated that map3k7cl in the leukocytes may contribute to pathogenesis via reducing inflammatory processes, regulating mitochondrial reactive oxygen species signaling, and mediating the Wnt pathway (56).…”