Abstract
BackgroundAtherosclerosis (AS) is the most common type in cardiovascular disease. Due to its complex pathogenesis, the exact etiology of AS is unclear. circRNA has been shown to play an essential role in most diseases. However, the underlying mechanism of circRNA in AS has been not understood clearly.MethodsQuantitative Real-Time PCR assay was used to detect the expression of circRSF1, miR-135b-5p and histone deacetylase 1 (HDAC1). Western blot was applied to the measure of protein expression of HDAC1, B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), cleaved-caspase-3, vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM1) and E-selectin. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Dual luciferase reporter assay and RIP assay was used to determine the relationship among circRSF1, miR-135b-5p and HDAC1. Besides, an ELISA assay was performed to measure the levels of IL-1β, IL-6, TNF-α and IL-8.ResultsIn this study, ox-LDL inhibited circRSF1 and HDAC1 expression while upregulated miR-135b-5p expression in Human umbilical vein endothelial cells (HUVECs). Importantly, ox-LDL could inhibit HUVECs growth. Moreover, promotion of circRSF1 or inhibition of miR-135b-5p induced cell proliferation while inhibited apoptosis and inflammation of ox-LDL-treated HUVECs, which was reversed by upregulating miR-135b-5p or downregulating HDCA1 in ox-LDL-treated HUVECs. More than that, we verified that circRSF1 directly targeted miR-135b-5p and HDAC1 was a target mRNA of miR-135b-5p in HUVECs.ConclusionCircRSF1 regulated ox-LDL-induced vascular endothelial cell proliferation, apoptosis and inflammation through modulating miR-135b-5p/HDAC1 axis in AS, providing new perspectives and methods for the treatment and diagnosis of AS.
Highlights
Atherosclerosis (AS) is one of the most common vascular diseases and is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease [1,2,3]
Through a series of cell physiology and biochemistry experiments, we demonstrated that circRSF1/miR-135b-5p/histone deacetylase 1 (HDAC1) axis played an essential role in AS, providing a new target and perspective for AS treatment
Ox‐low-density lipoprotein (LDL) inhibited circRSF1 expression in Human umbilical vein endothelial cells (HUVECs) CircRSF1 is derived from the remodeling and spacing factor 1 (RSF1) gene exon 10–11, and its mature sequence length is 1982 bp (Fig. 1a)
Summary
Atherosclerosis (AS) is one of the most common vascular diseases and is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease [1,2,3]. The pathogenesis of AS is not clear and has not yet. After oxidative modification, oxidative (ox)-LDL promoted AS more severely. Previous studies had shown that ox-LDL treatment inhibited the proliferation of vascular endothelial cells, promoted the apoptosis of endothelial cells, and induced the inflammation and oxidative stress of endothelial cells [4, 6, 7]. Atherosclerosis (AS) is the most common type in cardiovascular disease. Due to its complex pathogenesis, the exact etiology of AS is unclear. CircRNA has been shown to play an essential role in most diseases. The underlying mechanism of circRNA in AS has been not understood clearly
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