Zhao Kai, Zhu Guo-Zheng, Li Hong-Zhou, Gao Jia-Wen, Tu Chen, Wu Di-Zheng, Huang Yu-Sheng, Han Dong, Chen Xing-Yu, Wu Long-Yan, Zhong Zhao-Ming
Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Department of Orthopaedics, First Affiliated Hospital of Gannan Medical University, Ganzhou, People's Republic of China.
J Gerontol A Biol Sci Med Sci. 2024 Dec 11;80(1). doi: 10.1093/gerona/glae271.
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 was 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.
H型血管已被证实可将血管生成与骨生成联系起来。H型血管的减少会导致衰老过程中的骨质流失。衰老伴随着晚期氧化蛋白产物（AOPPs）的积累。然而，AOPPs积累是否参与了与年龄相关的H型血管减少尚不清楚。在此，我们表明老年小鼠血浆和骨骼中AOPPs水平的升高与H型血管的减少和骨量的丢失相关。微血管内皮细胞暴露于AOPPs会显著抑制细胞增殖、迁移和管腔形成；增加NADPH氧化酶活性并产生过量的活性氧；上调血管细胞黏附分子-1和细胞间黏附分子-1的表达；最终损害血管生成，而氧化还原调节剂N-乙酰半胱氨酸和NADPH氧化酶抑制剂夹竹桃麻素可缓解这一现象。此外，通过NAC处理减少AOPPs积累能够显著减轻老年小鼠H型血管的减少、骨量丢失和骨微结构的恶化。总的来说，这些发现表明AOPPs积累导致衰老过程中H型血管的减少，并揭示了与年龄相关的骨质流失的一种新的潜在机制。
