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 Ca2+ 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 idenepsied 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 idenepsy 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.
Highlights
Myocardial 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]
When compared with the small interfering RNA (siRNA)-mouse ATP2B1-AS1 group, the siRNA-mouse ATP2B1-AS1 + siRNA-nuclear factor-kappa-B inhibitor alpha (NFKBIA) group displayed a significant reduction in cell viability (P < .05). These results indicated that mouse ATP2B1-AS1 inhibited the growth of cardiomyocytes, while NFKBIA promoted the growth of cardiomyocytes, and the overexpression of NFKBIA could reverse the inhibition of cardiomyocyte activity triggered by the overexpression of mouse ATP2B1-AS1
The whole-genome transcriptome analysis has showed that many cardiac-specific Long non-coding RNAs (lncRNAs) involve in many unique functions and regulations related to myocardial remodelling, myocardial regeneration and heart function.[34]
Summary
Myocardial 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]. Nuclear factor-kappa-B inhibitor alpha (NFKBIA), known as IκBα, has the great potency to suppress nuclear factor-kappa B (NFκB).[11] NF-κB is a set of transcription factors, including RelB, c-Rel, NF-κB1 (p50), NF-κB2 (p52) and RelA (p65), that critically function as regulators in cell growth, cell apoptosis and immune inflammatory responses.[12] NF-κB has been shown to regulate approximately 200 target genes, and most of them are involved in inflammation.[13] In addition, NF-κB still exerts impacts on oxidative stress, genotoxic stress and the self-regulation of homeostatic functions.[14] Activated NF-κB signalling pathway can be observed in myocardial tissues from AMI mouse model, while impaired NF-κB signalling pathway could impede the cardiac rupture and ventricular remodelling.[15] investigations on the roles of lncRNAs and NF-κB and their interaction in MI are still limited. We investigated the roles of mouse ATP2B1-AS1 in MI through the regulation of the NFKBIA expression and NF-κB signalling pathway in mice
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