Expression of miRNAs Targeting ATP Binding Cassette Transporter 1 (ABCA1) among Patients with Significant Carotid Artery Stenosis

• Published in: Biomedicines Vol. 9; no. 8; p. 920
• Main Authors: Jeong, Seonjeong, Jun, Ji Hye, Kim, Jae Yeon, Park, Hee Jung, Cho, Yong-Pil, Kim, Gi Jin
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 30-07-2021; MDPI
• Subjects: ABCA1; ABCA1 protein; Asymptomatic; Atherosclerosis; ATP-binding protein; Biomarkers; Cardiovascular diseases; Carotid arteries; Carotid artery; carotid stenosis artery; Clinical outcomes; Disease; Endothelial cells; Enzyme-linked immunosorbent assay; Gene expression; Immunohistochemistry; Inflammation; Lipopolysaccharides; microRNA; MicroRNAs; miRNA; Palmitic acid; Patients; Plaques; Polymerase chain reaction; Proteins; Risk factors; Signal transduction; Stenosis; Stroke; Umbilical vein; Veins & arteries; United States > US
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines9080920

Background: Carotid artery stenosis is a dynamic process associated with an increased risk of cardiovascular events. However, knowledge of biomarkers useful for identifying and quantifying high-risk carotid plaques associated with the increased incidence of cerebrovascular events is insufficient. Therefore, the objectives of this study were to evaluate the expression of ATP binding cassette transporter 1 (ABCA1) and validate its target microRNA (miRNA) candidates in human carotid stenosis arteries to identify its potential as a biomarker. Methods: In human carotid stenosis arterial tissues and plasma, the expression of ABCA1 and its target miRNAs (miRNA-33a-5p, 33b-5p, and 148a-3p) were evaluated by quantitative real time-polymerase chain reaction (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Results: The expression of ABCA1 was significantly decreased in the plasma of stenosis patients, but its expression was not different in arterial tissues (p < 0.05). However, significantly more target miRNAs were secreted by stenosis patients than normal patients (p < 0.05). Interestingly, lipotoxicity induced by the oleic and palmitic acid (OAPA) or lipopolysaccharide (LPS) treatment of human umbilical vein endothelial cells (HUVECs) dramatically enhanced the gene expression of adipogenic and inflammatory factors, whereas ABCA1 expression was significantly decreased. Conclusions: Therefore, miRNA-33a-5p, 33b-5p, and 148a-3p represent possible biomarkers of carotid artery stenosis by directly targeting ABCA1.