Wang Zhenyu, Yao Chun, Huang Lihan, Liang Jianwen, Zhang Xiaocong, Shi Jian, Wei Wenbin, Zhou Jing, Zhang Yahui, Wu Guifu
Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
Department of Cardiology, Foshan Fosun Chancheng Hospital, Foshan, Guangdong, China.
Front Cardiovasc Med. 2023 Mar 2;10:1115494. doi: 10.3389/fcvm.2023.1115494. eCollection 2023.
This study aimed to investigate the therapeutic effect of enhanced external counterpulsation (EECP) on radial artery occlusion (RAO) through the oscillatory shear (OS) and pulsatile shear (PS) models of human umbilical vein endothelial cells (HUVECs) and RAO dog models.
We used high-throughput sequencing data GSE92506 in GEO database to conduct time-series analysis of functional molecules on OS intervened HUVECs, and then compared the different molecules and their functions between PS and OS. Additionally, we studied the effect of EECP on the radial artery hemodynamics in Labrador dogs through multi-channel physiological monitor. Finally, we studied the therapeutic effect of EECP on RAO at the histological level through Hematoxylin-Eosin staining, Masson staining, ATPase staining and immunofluorescence in nine Labrador dogs.
With the extension of OS intervention, the cell cycle decreased, blood vessel endothelial cell proliferation and angiogenesis responses of HUVECs were down-regulated. By contrast, the inflammation and oxidative stress responses and the related pathways of anaerobic metabolism of HUVECs were up-regulated. Additionally, we found that compared with OS, PS can significantly up-regulate muscle synthesis, angiogenesis, and NO production related molecules. Meanwhile, PS can significantly down-regulate inflammation and oxidative stress related molecules. The invasive arterial pressure monitoring showed that 30Kpa EECP treatment could significantly increase the radial artery peak pressure ( = 0.030, 95%CI, 7.236-82.524). Masson staining showed that RAO significantly increased muscle interstitial fibrosis ( = 0.002, 95%CI, 0.748-2.128), and EECP treatment can reduce this change ( = 0.011, 95%CI, -1.676 to -0.296). ATPase staining showed that RAO significantly increased the area of type II muscle fibers ( = 0.004, 95%CI, 7.181-25.326), and EECP treatment could reduce this change ( = 0.001, 95%CI, -29.213 to -11.069). In addition, immunofluorescence showed that EECP increased angiogenesis in muscle tissue ( = 0.035, 95%CI, 0.024-0.528).
EECP improves interstitial fibrosis and hypoxia, and increases angiogenesis of muscle tissue around radial artery induced by RAO.
本研究旨在通过人脐静脉内皮细胞(HUVECs)的振荡剪切(OS)和脉动剪切(PS)模型以及桡动脉闭塞(RAO)犬模型,探讨增强型体外反搏(EECP)对RAO的治疗效果。
我们使用GEO数据库中的高通量测序数据GSE92506对OS干预的HUVECs进行功能分子的时间序列分析,然后比较PS和OS之间不同的分子及其功能。此外,我们通过多通道生理监测仪研究EECP对拉布拉多犬桡动脉血流动力学的影响。最后,我们通过苏木精-伊红染色、Masson染色、ATP酶染色和免疫荧光,在9只拉布拉多犬身上从组织学水平研究EECP对RAO的治疗效果。
随着OS干预时间的延长,细胞周期缩短,HUVECs的血管内皮细胞增殖和血管生成反应下调。相比之下,HUVECs的炎症和氧化应激反应以及无氧代谢相关途径上调。此外,我们发现与OS相比,PS可显著上调肌肉合成、血管生成和一氧化氮产生相关分子。同时,PS可显著下调炎症和氧化应激相关分子。有创动脉压监测显示,30Kpa的EECP治疗可显著增加桡动脉峰值压力( = 0.030,95%CI,7.236 - 82.524)。Masson染色显示,RAO显著增加肌肉间质纤维化( = 0.002,95%CI,0.748 - 2.128),而EECP治疗可减轻这种变化( = 0.011,95%CI,-1.676至-0.296)。ATP酶染色显示,RAO显著增加II型肌纤维面积( = 0.004,95%CI,7.181 - 25.326),而EECP治疗可减轻这种变化( = 0.001,95%CI,-29.213至-11.069)。此外,免疫荧光显示EECP可增加肌肉组织中的血管生成( = 0.035,95%CI,0.024 - 0.528)。
EECP可改善间质纤维化和缺氧,并增加RAO诱导的桡动脉周围肌肉组织的血管生成。