Endothelial progenitor cells (EPCs) have been reported to replace the damaged endothelial cells to repair the injured or dead endothelium. However, EPC senescence might lead to the failure in EPC function. Thus, developing an in‐depth understanding of the mechanism of EPC senescence might provide novel strategies for related vascular disorders’ treatments. Herein, nicotinamide phosphoribosyltransferase (NAMPT) overexpression could increase cell proliferation and suppress cell senescence in EPCs. miR‐223 directly bound to the 3′‐untranslated region of NAMPT to inhibit its expression, therefore modulating EPC proliferation and senescence through NAMPT and phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) signaling. Long noncoding RNA (lncRNA) GAS5 sponges miR‐223, consequently downregulating miR‐223 expression. GAS5 knockdown inhibited EPC proliferation and promoted senescence. GAS5 might serve as a competing endogenous RNA for miR‐223 to counteract miR‐223‐mediated suppression on NAMPT, thus regulating EPC proliferation and senescence via the PI3K/AKT signaling pathway. In summary, our findings provide a solid experimental basis for understanding the role and mechanism of lncRNA GAS5/miR‐223/NAMPT axis in EPC proliferation and senescence.

Pre-B cell colony-enhancing factor (PBEF) has been shown to have a variety of biological functions. Studies have proven that PBEF plays a functional role in acute lung injury (ALI). Therefore, in this study, we aimed to confirm the importance of PBEF in ALI. The effects of PBEF overexpression on the apoptosis of human pulmonary microvascular endothelial cells (HPMECs) were analyzed by flow cytometry, and the results indicated that PBEF promoted the apoptosis of HPMECs, which aggravated the development of ALI. Comparative experiments involving increasing and decreasing PBEF expression demonstrated that PBEF promoted the expression of inflammatory factors, such as interleukin (IL)‑1β, IL‑6 and IL‑8 in the HPMECs , thus intensifying the inflammatory response. PBEF also inhibited the expression of aquaporin 1 (AQP1), which caused a dysfunction and imbalance in water transport. Moreover, we also found that tumor necrosis factor (TNF)‑α promoted the expression of PBEF in the HPMECs. After blocking the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, we found that PBEF regulated the expression of inflammatory factors and AQP1, mainly through the MAPK pathways. Taken together, these results demonstrate that the increase in intracellular PBEF expression promoted the apoptosis of HPMECs and the expression of inflammatory factors and thus enhanced the inflammatory response and inhibited the expression of AQP1, which resulted in abnormal water transport, diminishing the regulatory effects of AQP1 on water transport.

Endothelial dysfunction participates in the pathogenesis of various cardiovascular disorders, and dysregulated angiogenesis involves the vascular endothelial growth factor (VEGF)–matrix metalloproteinases (MMP) system. Nicotinamide phosphoribosyltransferase (NAMPT) is known to enhance endothelial function and angiogenesis. The study found that NAMPT overexpression protected human coronary artery endothelial cells (HCAECs) from H2O2-induced injury through promoting cell viability, inhibiting cell apoptosis, enhancing cell motility, and promoting tube formation. Through analyses based on 2 Protein–Protein Interaction databases, Mentha and BioGrid, we identified CUL5 as a protein that may interact with NAMPT, which was then validated by Co-IP experiments. Through interacting with NAMPT, CUL5 inhibited NAMPT expression. In contrast to NAMPT, CUL5 overexpression further aggravated H2O2-induced HCAEC dysfunction. In the meantime, CUL5 overexpression reduced, whereas NAMPT overexpression increased the phosphorylation of p38 and Akt and the protein levels of VEGF and MMP2. More importantly, NAMPT overexpression partially reversed the effects of CUL5 overexpression on H2O2-stimulated HCAECs and the MAPK/phosphatidylinositol 3-kinase-Akt/VEGF/MMP signaling. In conclusion, CUL5 interacts with NAMPT in H2O2-stimulated HCAECs, suppressing cell viability, promoting cell apoptosis, and inhibiting cell mobility and tube formation. NAMPT overexpression protects against H2O2-induced HCAEC dysfunction by promoting cell viability, inhibiting cell apoptosis, and enhancing cell mobility and tube formation.