Silencing of lncRNA TFAP2A-AS1 attenuates the development of acute coronary syndrome by inhibiting TFAP2A expression

抑制lncRNA TFAP2A-AS1可通过抑制TFAP2A表达来减轻急性冠脉综合征的发生发展。

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Abstract

Acute coronary syndrome (ACS), the acute manifestation of ischemic heart disease, remains a major cause of morbidity and mortality worldwide. The present study aimed to elucidate the preliminarily biological role and underlying mechanism of the long non-coding RNA (lncRNA) transcription factor AP-2α (TFAP2A)-AS1 in ACS. The viability, apoptosis, invasion, and migration of human coronary artery endothelial cells (HCAECs) were assessed using Cell Counting Kit-8, flow cytometric, Transwell, and wound healing assays. In addition, reverse transcription-quantitative PCR was performed to examine the expression levels of TFAP2A-AS1 and TFAP2A. Western blotting was performed to determine the protein level of TFAP2A. Furthermore, a mouse model of ACS was established to investigate the effects of TFAP2A-AS1 and TFAP2A on blood lipid levels. Histological changes were evaluated through hematoxylin and eosin staining. The results revealed high levels of TFAP2A-AS1 and TFAP2A expression in patients with ACS and in mouse models. In HCAECs, knockdown of TFAP2A-AS1 resulted in decreased TFAP2A expression, whereas silencing of TFAP2A did not affect the expression of TFAP2A-AS1. Interference with either TFAP2A-AS1 or TFAP2A in HCAECs led to suppressed cell viability, invasion, and migration, as well as an increased apoptosis rate. Furthermore, it was demonstrated that the absence of both TFAP2A-AS1 and TFAP2A reduced blood lipid levels and improved myocardial injury in a mouse model of ACS. In conclusion, groundbreaking findings revealed that the suppression of TFAP2A-AS1 could effectively mitigate the progression of ACS by reducing the expression of TFAP2A. This finding not only offers crucial insight into the pathogenesis of ACS but also provides a solid theoretical foundation for the development of novel therapeutic interventions in clinical settings.

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