Dou Fangfang, Wu Beiling, Chen Jiulin, Liu Te, Yu Zhihua, Chen Chuan
Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, China.
Oxid Med Cell Longev. 2021 Feb 25;2021:2045259. doi: 10.1155/2021/2045259. eCollection 2021.
Atherosclerosis (AS) is a complex vascular disease that seriously harms the health of the elderly. It is closely related to endothelial cell aging, but the role of senescent cells in atherogenesis remains unclear. Studies have shown that peroxisome proliferator-activated receptor alpha (PPAR) inhibits the development of AS by regulating lipid metabolism. Our previous research showed that PPAR was involved in regulating the repair of damaged vascular endothelial cells. Using molecular biology and cell biology approaches to detect senescent cells in atherosclerosis-prone apolipoprotein E-deficient ( ) mice, we found that PPAR delayed atherosclerotic plaque formation by inhibiting vascular endothelial cell senescence, which was achieved by regulating the expression of growth differentiation factor 11 (GDF11). GDF11 levels declined with age in several organs including the myocardium, bone, central nervous system, liver, and spleen in mice and participated in the regulation of aging. Our results showed that PPAR inhibited vascular endothelial cell senescence and apoptosis and promoted vascular endothelial cell proliferation and angiogenesis by increasing GDF11 production. Taken together, these results demonstrated that PPAR inhibited vascular endothelial cell aging by promoting the expression of the aging-related protein GDF11, thereby delaying the occurrence of AS.
动脉粥样硬化（AS）是一种严重危害老年人健康的复杂血管疾病。它与内皮细胞衰老密切相关，但衰老细胞在动脉粥样硬化发生过程中的作用仍不清楚。研究表明，过氧化物酶体增殖物激活受体α（PPAR）通过调节脂质代谢抑制AS的发展。我们之前的研究表明，PPAR参与调节受损血管内皮细胞的修复。利用分子生物学和细胞生物学方法检测易患动脉粥样硬化的载脂蛋白E缺陷（ ）小鼠中的衰老细胞，我们发现PPAR通过抑制血管内皮细胞衰老来延迟动脉粥样硬化斑块形成，这是通过调节生长分化因子11（GDF11）的表达实现的。在小鼠的几个器官中，包括心肌、骨骼、中枢神经系统、肝脏和脾脏，GDF11水平随年龄下降并参与衰老调节。我们的结果表明，PPAR通过增加GDF11的产生来抑制血管内皮细胞衰老和凋亡，并促进血管内皮细胞增殖和血管生成。综上所述，这些结果表明PPAR通过促进衰老相关蛋白GDF11的表达来抑制血管内皮细胞衰老，从而延缓AS的发生。
