The aim of the present study was to investigate the potential role of regulated in development and DNA damage response 1 (REDD1) in LPS-induced vascular endothelial injury by using human umbilical vein endothelial cells (HUVECs). We observed that REDD1 expression was apparently elevated in HUVECs after exposure to LPS. Additionally, elimination of REDD1 strikingly attenuated the secretion of the proinflammatory cytokines TNF-α, IL-6, IL-1β, and monocyte chemotactic protein-1 and the endothelial cell adhesion markers ICAM-1 and VCAM-1 that was induced by LPS stimulation. Subsequently, knockdown of REDD1 augmented cell viability but ameliorated lactate dehydrogenase release in HUVECs stimulated with LPS. Meanwhile, depletion of REDD1 effectively restricted LPS-induced HUVEC apoptosis, as exemplified by reduced DNA fragmentation, and it also elevated antiapoptotic Bcl-2 protein, concomitant with reduced levels of proapoptotic proteins Bax and cleaved caspase-3. Furthermore, repression of REDD1 remarkably alleviated LPS-triggered intracellular reactive oxygen species generation accompanied by decreased malondialdehyde content and increased the activity of the endogenous antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. Most important, depletion of REDD1 protected HUVECs against inflammation-mediated apoptosis and oxidative damage partly through thioredoxin-interacting protein (TXNIP). Collectively, these findings indicate that blocking the REDD1/TXNIP axis repressed the inflammation-mediated vascular injury process, which may be closely related to oxidative stress and apoptosis in HUVECs, implying that the REDD1/TXNIP axis may be a new target for preventing the endothelial cell injury process.
microRNAs (miRNAs) have been revealed to participate in the pathological process of atherosclerosis (AS). However, the exact role of miR‐338‐3p, a target miRNA of BMP and activin membrane‐bound inhibitor (BAMBI), and its possible molecular mechanism in AS remain unidentified. In this study, we found that BAMBI was significantly decreased, whereas miR‐338‐3p increased in patients with AS and oxidized low‐density lipoprotein (ox‐LDL)‐induced HUVEC cells. Furthermore, overexpression of miR‐338‐3p significantly decreased cell viability and elevated cell apoptosis, whereas its inhibition significantly promoted cell viability and inhibited cell apoptosis in ox‐LDL‐induced HUVEC cells. Moreover, miR‐338‐3p overexpression increased TGF‐β/Smad pathway activation in ox‐LDL‐induced HUVEC cells. A dual‐luciferase reporter assay confirmed the direct interaction between miR‐338‐3p and the 3′‐untranslated region of BAMBI messenger RNA. Furthermore, the suppression of BAMBI ameliorated the effect of miR‐338‐3p inhibition against ox‐LDL‐induced HUVEC cell injury. In conclusion, our study thus suggests that miR‐338‐3p promoted ox‐LDL‐induced HUVEC cell injury by targeting BAMBI and activating the TGF‐β/Smad pathway, which may provide a novel and promising therapeutic target for AS.
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