羟基红花黄色素 A 通过激活 HIF-1α-VEGFA-Notch1 信号通路促进血管生成并减轻心肌缺血再灌注损伤。
The activation of the HIF-1α-VEGFA-Notch1 signaling pathway by Hydroxysafflor yellow A promotes angiogenesis and reduces myocardial ischemia-reperfusion injury.
机构信息
Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of Chinese Medicine, Hefei 230012, China; Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Traditional Chinese Medicine, Hefei 230012, China.
Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of Chinese Medicine, Hefei 230012, China; Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Traditional Chinese Medicine, Hefei 230012, China.
出版信息
Int Immunopharmacol. 2024 Dec 5;142(Pt A):113097. doi: 10.1016/j.intimp.2024.113097. Epub 2024 Sep 10.
UNLABELLED
Hydroxyl Safflower Yellow A (HSYA) is the primary bioactive compound derived from Safflower, which has been scientifically proven to possess anti-inflammatory, anti-apoptotic, and ameliorative properties against mitochondrial damage during acute myocardial ischemia-reperfusion injury (MIRI); however, its effects during the recovery stage remain unknown. Angiogenesis plays a crucial role in the rehabilitation process.
AIM OF THE STUDY
The objective of this study was to investigate the long-term angiogenic effect of HSYA and its contribution to recovery after myocardial ischemia, as well as explore its underlying mechanism using non-targeted metabolomics and network pharmacology.
MATERIALS AND METHODS
The MIRI model in rat was established by ligating the left anterior descending branch of the coronary artery. The effect of HSYA was assessed based on myocardial infarction volume and histopathology. Immunofluorescence staining was employed to evaluate angiogenesis, while ELISA was used to detect markers of myocardial injury. Additionally, a rat myocardial microvascular endothelial cell (CMECs) injury model was established using oxygen-glucose deprivation/reoxygenation (OGD/R), followed by scratch assays, migration assays, and tube formation experiments to assess angiogenesis. Western blot analysis was conducted to validate the underlying mechanism.
RESULTS
Our findings provide compelling evidence for the therapeutic efficacy of HSYA in reducing myocardial infarction size, facilitating cardiac functional recovery, and reversing pathological alterations within the heart. Furthermore, we elucidate that HSYA exerts its effects on promoting migration and generation of myocardial microvascular endothelial cells through activation of the HIF-1α-VEGFA-Notch1 signaling pathway.
CONCLUSION
These results underscore how HSYA enhances cardiac function via angiogenesis promotion and activation of the aforementioned signaling cascade.
目的
本研究旨在探讨羟基红花黄色素 A（HSYA）的长期促血管生成作用及其在心肌缺血再灌注损伤（MIRI）后恢复中的作用，并通过非靶向代谢组学和网络药理学方法探讨其潜在机制。
材料和方法
结扎大鼠冠状动脉左前降支建立 MIRI 模型，根据心肌梗死面积和组织病理学评估 HSYA 的作用。免疫荧光染色评估血管生成，ELISA 检测心肌损伤标志物。此外，采用氧葡萄糖剥夺/复氧（OGD/R）建立大鼠心肌微血管内皮细胞（CMECs）损伤模型，划痕实验、迁移实验和管形成实验评估血管生成。Western blot 分析验证潜在机制。
结果
我们的研究结果为 HSYA 通过减少心肌梗死面积、促进心脏功能恢复和逆转心脏内的病理改变来发挥治疗功效提供了有力证据。此外，我们阐明 HSYA 通过激活 HIF-1α-VEGFA-Notch1 信号通路来发挥作用，促进心肌微血管内皮细胞的迁移和生成。
结论
这些结果强调了 HSYA 通过促进血管生成和激活上述信号级联来增强心脏功能。
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