The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Cheeloo College of Medicine, Qilu Hospital, Shandong University, Jinan, China.
J Cell Mol Med. 2021 Aug;25(16):7760-7771. doi: 10.1111/jcmm.16661. Epub 2021 Jun 27.
Lymphangiogenesis is possibly capable of attenuating hypertension-induced cardiac injury. Sirtuin 3 (SIRT3) is an effective mitochondrial deacetylase that has the potential to modulate this process; however, its role in hypertension-induced cardiac lymphangiogenesis to date has not been investigated. Our experiments were performed on 8-week-old wild-type (WT), SIRT3 knockout (SIRT3-KO) and SIRT3 overexpression (SIRT3-LV) mice infused with angiotensin II (Ang II) (1000 ng/kg per minute) or saline for 28 days. After Ang II infusion, SIRT3-KO mice developed a more severe cardiac remodelling, less lymphatic capillaries and lower expression of lymphatic marker when compared to wild-type mice. In comparison, SIRT3-LV restored lymphangiogenesis and attenuated cardiac injury. Furthermore, lymphatic endothelial cells (LECs) exposed to Ang II in vitro exhibited decreased migration and proliferation. Silencing SIRT3 induced functional decrease in LECs, while SIRT3 overexpression LECs facilitated. Moreover, SIRT3 may up-regulate lymphangiogenesis by affecting vascular endothelial growth factor receptor 3 (VEGFR3) and ERK pathway. These findings suggest that SIRT3 could promote lymphangiogenesis and attenuate hypertensive cardiac injury.
淋巴管生成可能能够减轻高血压引起的心脏损伤。沉默信息调节因子 3（SIRT3）是一种有效的线粒体去乙酰化酶，具有调节此过程的潜力；然而，其在高血压引起的心脏淋巴管生成中的作用尚未得到研究。我们的实验在 8 周龄的野生型（WT）、SIRT3 敲除（SIRT3-KO）和 SIRT3 过表达（SIRT3-LV）小鼠上进行，这些小鼠接受血管紧张素 II（Ang II）（1000ng/kg/min）或生理盐水输注 28 天。Ang II 输注后，与野生型小鼠相比，SIRT3-KO 小鼠表现出更严重的心脏重塑、更少的淋巴管毛细血管和更低的淋巴管标记物表达。相比之下，SIRT3-LV 恢复了淋巴管生成并减轻了心脏损伤。此外，体外暴露于 Ang II 的淋巴管内皮细胞（LECs）表现出迁移和增殖减少。沉默 SIRT3 诱导 LECs 的功能下降，而过表达 SIRT3 则促进 LECs 的功能。此外，SIRT3 可能通过影响血管内皮生长因子受体 3（VEGFR3）和 ERK 通路来促进淋巴管生成。这些发现表明 SIRT3 可以促进淋巴管生成并减轻高血压性心脏损伤。
