Oxidized Low Density Lipoprotein-Induced Atherogenic Response of Human Umbilical Vascular Endothelial Cells (HUVECs) was Protected by Atorvastatin by Regulating miR-26a-5p/Phosphatase and Tensin Homolog (PTEN)

Abstract

Background: Atherosclerosis is a chronic and multifactorial disease, and it is the main reason of coronary heart disease, cerebral infarction, and peripheral vascular disease, which leads to the formation of lesions in arterial blood vessels. Our study aimed to explore the protective effect and its underlying mechanism of atorvastatin (ATV) on oxidized low-density lipoprotein (ox-LDL)-induced atherosclerosis. Material/Methods: Human umbilical vascular endothelial cells (HUVECs) were cultured and pretreated with ox-LDL to establish an in vitro atherosclerotic cell model. Cell Counting Kit-8 (CCK-8) assay, TUNEL staining, and Transwell assay were used to detect the cell activity, apoptosis, and migration in HUVECs. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied to measure the mRNA and protein expressions of adhesionrelated genes in HUVECs. Results: Pretreated with 100 mg/L ox-LDL resulted in a 57.23% decrease of cell viability and 81.09% increase of apoptotic injury in HUVECs compare to the control. Meanwhile, ox-LDL pretreatment increased the cell migration and the expression of miR-26a-5p in HUVECs. ATV treatment could effectively reverse the cellular damage induced by ox-LDL, decrease the release of adhesion-related molecules, and downregulate the expression of miR-26a-5p by 44.79% in HUVECs. Moreover, phosphatase and tensin homolog (PTEN) was demonstrated to be the target gene of miR-26a-5p. Conclusions: Our results highlight that ATV protects against ox-LDL-induced downregulation of cell viability, upregulation of cell apoptosis, migration, as well as the release of adhesion-related molecules in HUVECs through the miR-26a-5p/PTEN axis. This study provides new insights into the underlying mechanism of ATV therapeutic potential in atherosclerosis, and also provides a new strategy for the treatment of atherosclerosis.

Synovial mesenchymal stem cell‐derived extracellular vesicles containing microRN555A‐26a‐5p ameliorate cartilage damage of osteoarthritis

“…A database found that miR‐26a‐5p targets PTEN. The target relationship of miR‐26a‐5p and PTEN has been reported in previous studies 39,40 . Notably, the positive function of miR‐26a‐5p in facilitating fibroblast‐like synoviocyte transition and migration and preventing rheumatoid arthritis was largely depended on its inhibition of PTEN 29 .…”

MiR‐26a‐5p alleviates cardiac hypertrophy and dysfunction via targeting ADAM17

“…MiR‐26a‐5p was downregulated by circular RNA ciRS‐7 in atherosclerosis (Cui et al, 2020). Atorvastatin (ATV) prevented atherosclerosis through miR‐26a‐5p/PTEN signaling (Jia et al, 2019).…”

Hsa_circ_0004831 downregulation is partially responsible for atorvastatinalleviated human umbilical vein endothelial cell injuries induced by ox-LDL through targeting the miR-182-5p/CXCL12 axis

“…Besides, ATV weakened the extent of local inflammation in atherosclerotic plaques to combat AS [ 19 ]. Moreover, ATV treatment blocked the apoptotic rate and the migration ability in ox-LDL-administered HUVECs [ 20 ]. ATV usage regulated the expression of inflammatory and oxidant markers (the decrease of C-reactive protein and Myeloperoxidase, and the increase of SOD) in plasma samples of AS patients [ 21 ].…”