Citronellal can alleviate vascular endothelial dysfunction by reducing ectopic miR-133a expression

Aims: Endothelial dysfunction (ED) is the initial cause of atherosclerosis (AS) and an early marker of many cardiovascular diseases (CVD). Citronellal (CT), a monoterpenoid natural product extracted from grass plant Citronella, has been shown to have anti-thrombotic, anti-hypertensive and anti-diabetic cardiomyopathy activities. The aim of this study is to investigate the effects of citronellal on vascular endothelial dysfunction and the underlying mechanisms. Materials and methods: The left common carotid artery was subjected to one-time balloon injury to cause vascular endothelial injury, and the AS model was established by feeding with high-fat diet. Use of HUVECs H2O2 treatment induced HUVECs oxidative stress damage model. The blood lipid level, histopathology, Western blot, immunohistochemistry, RT-PCR, ELISA and in situ fluorescence hybridization of common carotid artery tissues and HUVECs were studied. Key findings: CT significantly reduced vascular plate area and endothelial lipid and cholesterol deposition in the common carotid artery of mice in a dose-dependent manner. CT increased the expression of activated protein 2 alpha (AP-2 alpha/TFAP2A) and circRNA_102979, and inhibited the ectopic expression level of miR-133a. However, the constructed lentivirus with AP-2 alpha silencing and circRNA_102979 silencing reversed this phenomenon. Significance: The current study verifies CT can increase the expression levels of AP-2 alpha and circRNA_102979 in vascular endothelium, increase the adsorption effect of circRNA_102979 on miR-133a and relieve the inhibitory effect of miR-133a on target genes, thereby alleviating AS-induced ED.