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

Life Sci

Department of Pharmacy, Beijing Renhe Hospital, Beijing 102600, China; Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China; Key Laboratory of Diabetes and Angiopathy, Hubei University of Science and Technology, Xianning 437100, China. Electronic address:

Published: February 2024

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 HO 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 2α (AP-2α/TFAP2A) and circRNA_102979, and inhibited the ectopic expression level of miR-133a. However, the constructed lentivirus with AP-2α silencing and circRNA_102979 silencing reversed this phenomenon.

Significance: The current study verifies CT can increase the expression levels of AP-2α 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.

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http://dx.doi.org/10.1016/j.lfs.2023.122382DOI Listing

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