MiR‐29a mediates the apoptotic effects of TNF‐α on endothelial cells through inhibiting PI3K/AKT/BCL‐2 axis

• Published in: Journal of biochemical and molecular toxicology Vol. 38; no. 1; pp. e23598 - n/a
• Main Authors: Cao, Yunchang, Wen, Hongbo, Leng, Chaoqun, Feng, Shaolong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2024
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; Arteriosclerosis; Atherosclerosis; atherosclerosis (AS); Atherosclerosis - metabolism; Cardiovascular diseases; Cell proliferation; Complications; Endothelial cells; human umbilical vascular endothelial cells (HUVECs); Human Umbilical Vein Endothelial Cells - metabolism; Humans; Inflammation; Inflammation - metabolism; microRNA (miR)‐29a; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Molecular modelling; Pathogenesis; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Signal transduction; Target detection; Therapeutic targets; Time dependence; tumor necrosis factor (TNF)‐α; Tumor Necrosis Factor-alpha - metabolism; Up-regulation; apoptosis; microRNA (miR)-29a; atherosclerosis (AS); human umbilical vascular endothelial cells (HUVECs); tumor necrosis factor (TNF)-α
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.23598

Endothelial cell apoptosis driven by inflammation (TNF‐α) plays a critical role in the pathogenesis of atherosclerosis, but the exact molecular mechanisms are not clearly elucidated. MicroRNA (miR)‐29 families (a/b/c) take important roles in pathophysiological processes of atherosclerosis, also the underlying mechanisms have not been fully clarified. The aims are to explore whether or not miR‐29 families mediate the apoptotic effects of TNF‐α on endothelial cells and uncover the underlying molecular mechanisms. In this study, MTT assay and flow cytometer analysis were employed respectively to determine the proliferation and apoptosis of human umbilical vascular endothelial cells (HUVECs) under TNF‐α exposure. Real‐time quantitative PCR and western blot were performed to detect the levels of target RNAs and proteins/their phosphorylation in HUVECs. TNF‐α could inhibit HUVEC proliferation and induce HUVEC apoptosis in a positive dose‐ and time‐dependent manner, with a similar way of miR‐29a upregulation, but no effects on miR‐29b/c. Upregulation of miR‐29a with its mimics enhanced the apoptotic effect of TNF‐α on HUVECs, but downregulation of miR‐29a using anti‐miR‐29a blocked up its apoptotic effect. MiR‐29a inhibited the expression of PI3Kp85α and Bcl‐2 and blocked up the signal transduction of PI3K/AKT/Bcl‐2 axis to mediate the apoptotic effect of TNF‐α on HUVECs. Mediating the inflammation‐driven endothelial cell apoptosis is an important biology mechanism by which miR‐29a promotes atherosclerosis and its complications. MiR‐29a will be a potential diagnostic and therapeutic target for atherosclerotic cardiovascular diseases; it is worthwhile to further study. The signal pathway of TNF‐α inducing human umbilical vascular endothelial cells apoptosis.