Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Lishui, Zhejiang, China ; and.
J Cardiovasc Pharmacol. 2021 Mar 1;77(3):408-417. doi: 10.1097/FJC.0000000000000967.
Promoting angiogenesis is a critical treatment strategy for ischemic cardiovascular diseases. Shexiang Baoxin Pill (SBP), a traditional Chinese medicine, has been reported to be capable of relieving angina and improve heart function by promoting angiogenesis. The aim of this study was to determine the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in SBP-induced angiogenesis. Left femoral artery ligation was performed in wild-type mice (WT) and ALDH2 knockout mice, which were administrated with SBP (20 mg/kg/d) or equal volume saline per day by gastric gavage for 2 weeks. Perfusion recovery, angiogenesis in chronic hind limb ischemia, was significantly improved in the WT + SBP group than in the WT group. However, these beneficial effects were absent in ALDH2 knockout mice. In vitro, hypoxia impaired the ability of proliferation, migration and tube formation, sprouting angiogenesis, and promoted apoptosis in cardiovascular microvascular endothelial cells, whereas the hypoxia damage was restored by SBP. The protective effect of SBP was remarkably weakened by ALDH2 knockdown. Furthermore, SBP suppressed hypoxia-induced ALDH2/protein kinase B (AKT)/mammalian target of rapamycin pathways. In conclusion, this study demonstrated that SBP protected lower limb from ischemia injury through the ALDH2-dependent pathway. The protective mechanism of SBP in cardiovascular microvascular endothelial cells was partly mediated through ALDH2/AKT/mammalian target of rapamycin pathways.
促进血管生成是缺血性心血管疾病的一种重要治疗策略。麝香保心丸（SBP）是一种中药，据报道可通过促进血管生成缓解心绞痛和改善心脏功能。本研究旨在确定线粒体乙醛脱氢酶 2（ALDH2）在 SBP 诱导的血管生成中的作用。在野生型小鼠（WT）和 ALDH2 敲除小鼠中进行左侧股动脉结扎，每天通过胃灌胃给予 SBP（20mg/kg/d）或等体积生理盐水 2 周。WT+SBP 组的灌流恢复和慢性后肢缺血中的血管生成明显优于 WT 组。然而，这些有益作用在 ALDH2 敲除小鼠中不存在。在体外，缺氧会损害增殖、迁移和管状形成、发芽血管生成以及促进心血管微血管内皮细胞凋亡的能力，而 SBP 则恢复了缺氧损伤。SBP 对 ALDH2 敲低的保护作用明显减弱。此外，SBP 抑制了缺氧诱导的 ALDH2/蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白途径。总之，本研究表明 SBP 通过 ALDH2 依赖性途径保护下肢免受缺血性损伤。SBP 在心血管微血管内皮细胞中的保护机制部分通过 ALDH2/AKT/哺乳动物雷帕霉素靶蛋白途径介导。
