Endothelial dysfunction participates in the pathogenesis of various cardiovascular disorders, and dysregulated angiogenesis involves the vascular endothelial growth factor (VEGF)-matrix metalloproteinases (MMP) system. NAMPT (Nicotinamide phosphoribosyltransferase) is known to enhance endothelial function and angiogenesis. The study found that NAMPT overexpression protected human coronary artery endothelial cells from H2O2-induced injury through promoting cell viability, inhibiting cell apoptosis, enhancing cell motility, and promoting tube formation. Through analyses based on two Protein-Protein Interaction databases, Mentha and BioGrid, we identified CUL5 as a protein that might 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/PI3K-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.

中文翻译：

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CUL5 介导的 Visfatin (NAMPT) 降解通过 MAPK/PI3K-AKT 信号传导阻断内皮增殖和血管生成。

内皮功能障碍参与各种心血管疾病的发病机制，血管生成失调涉及血管内皮生长因子（VEGF）-基质金属蛋白酶（MMP）系统。NAMPT（烟酰胺磷酸核糖转移酶）已知可增强内皮功能和血管生成。研究发现，NAMPT 过表达通过促进细胞活力、抑制细胞凋亡、增强细胞运动和促进管形成，保护人冠状动脉内皮细胞免受 H2O2 诱导的损伤。通过基于 Mentha 和 BioGrid 两个蛋白质-蛋白质相互作用数据库的分析，我们确定 CUL5 是一种可能与 NAMPT 相互作用的蛋白质，然后通过 Co-IP 实验进行验证。通过与 NAMPT 相互作用，CUL5 抑制 NAMPT 表达。与 NAMPT 相比，CUL5 过表达进一步加剧了 H2O2 诱导的 HCAEC 功能障碍。同时，CUL5过表达减少，而NAMPT过表达增加p38和Akt的磷酸化以及VEGF和MMP2的蛋白水平。更重要的是，NAMPT 过表达部分逆转了 CUL5 过表达对 H2O2 刺激的 HCAEC 和 MAPK/PI3K-Akt/VEGF/MMP 信号传导的影响。总之，CUL5 在 H2O2 刺激的 HCAEC 中与 NAMPT 相互作用，抑制细胞活力，促进细胞凋亡，并抑制细胞迁移和管形成。NAMPT 过表达通过促进细胞活力、抑制细胞凋亡、增强细胞迁移性和管形成来防止 H2O2 诱导的 HCAEC 功能障碍。