Abstract
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.
Highlights
The higher degree of carotid artery stenosis is linked to a higher risk of ipsilateral neurologic events, and significant carotid artery stenosis accounts for about 30% of ischemic strokes with an annual risk of ipsilateral stroke of1–3% [1,2,3]
The ability of human umbilical vein endothelial cells (HUVECs) to develop vascular structure was sharply reduced by treatment with oleic and palmitic acid (OAPA) and LPS. It was significantly recovered by transfection of the miRNA inhibitors (p < 0.05, Revised Figure 9A,C). These results demonstrated that ATP Binding Cassette Transporter 1 (ABCA1) was decreased in damaged HUVECs, whereas the expression of its target miRNAs was increased by directly targeting ABCA1 in the HUVECs
One of several proteins related to cholesterol homeostasis is ATP Binding Cassette Transporter 1 (ABCA1), a transmembrane protein extensively expressed in many tissues [25]
Summary
The higher degree of carotid artery stenosis is linked to a higher risk of ipsilateral neurologic events, and significant carotid artery stenosis (greater than 50% diameter reduction) accounts for about 30% of ischemic strokes with an annual risk of ipsilateral stroke of1–3% [1,2,3]. There is little knowledge on biomarkers that is useful for identifying and quantifying high-risk carotid plaques associated with the increased incidence of cerebrovascular events. Carotid artery stenosis is a dynamic process associated with an increased risk of cardiovascular events. Knowledge of biomarkers useful for identifying and quantifying high-risk carotid plaques associated with the increased incidence of cerebrovascular events is insufficient. 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 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
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