Type H vessels have been proven to couple angiogenesis and osteogenesis. The decline of type H vessels contributes to bone loss in the aging process. Aging is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, whether AOPP accumulation is involved in age-related decline of type H vessels is unclear. Here, we show that the increase of AOPP levels in plasma and bone were correlated with the decline of type H vessels and loss of bone mass in old mice. Exposure of microvascular endothelial cells to AOPPs significantly inhibited cell proliferation, migration, and tube formation, increased NADPH oxidase activity and excessive reactive oxygen species generation, upregulated the expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1, and eventually impaired angiogenesis, which was alleviated by redox modulator N-acetylcysteine and NADPH oxidase inhibitor apocynin. Furthermore, reduced AOPP accumulation by NAC treatment was able to alleviate significantly the decline of type H vessels, bone mass loss and deterioration of bone microstructure in old mice. Collectively, these findings suggest that AOPPs accumulation contributes to the decline of type H vessels in the aging process, and illuminate a novel potential mechanism underlying age-related bone loss.

中文翻译：

---

高级氧化蛋白产物的积累促进了骨骼中 H 型血管的年龄相关性下降


H 型血管已被证明可以耦合血管生成和成骨。H 型血管的衰退会导致衰老过程中的骨质流失。衰老伴随着高级氧化蛋白产物 （AOPP） 的积累。然而，AOPP 积累是否与年龄相关的 H 型血管下降有关尚不清楚。在这里，我们表明血浆和骨骼中 AOPP 水平的增加与老年小鼠 H 型血管的减少和骨量的损失相关。微血管内皮细胞暴露于 AOPPs 显著抑制细胞增殖、迁移和管形成，增加 NADPH 氧化酶活性和过量活性氧生成，上调血管细胞粘附分子-1 和细胞间细胞粘附分子-1 的表达，最终损害血管生成，氧化还原调节剂 N-乙酰半胱氨酸和 NADPH 氧化酶抑制剂阿波辛减轻。此外，NAC 处理减少 AOPP 积累能够显着缓解老年 小鼠 H 型血管的下降、骨量损失和骨微结构的恶化。总的来说，这些发现表明 AOPPs 积累有助于衰老过程中 H 型血管的衰退，并阐明了与年龄相关的骨质流失的新潜在机制。