Smorodintsev Research Institute of Influenza, Russian Ministry of Health, 197376 St. Petersburg, Russia.
Smorodintsev Research Institute of Influenza, Department of Medical Microbiology, North-Western State Medical University Named after I.I. Mechnikov, 191015 St. Petersburg, Russia.
Viruses. 2023 May 4;15(5):1114. doi: 10.3390/v15051114.
Influenza virus can infect the vascular endothelium and cause endothelial dysfunction. Persons at higher risk for severe influenza are patients with acute and chronic cardiovascular disorders; however, the mechanism of influenza-induced cardiovascular system alteration remains not fully understood. The aim of the study was to assess the functional activity of mesenteric blood vessels of Wistar rats with premorbid acute cardiomyopathy infected with Influenza A(H1N1)pdm09 virus. For this, we determined (1) the vasomotor activity of mesenteric blood vessels of Wistar rats using wire myography, (2) the level of expression of three endothelial factors: endothelial nitric oxide synthase (eNOS), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) in the endothelium of mesenteric blood vessels using immunohistochemistry, and (3) the concentration of PAI-1 and tPA in the blood plasma using ELISA. Acute cardiomyopathy in animals was induced by doxorubicin (DOX) following infection with rat-adapted Influenza A(H1N1)pdm09 virus. The functional activity of mesenteric blood vessels was analyzed at 24 and 96 h post infection (hpi). Thus, the maximal response of mesenteric arteries to both vasoconstrictor and vasodilator at 24 and 96 hpi was significantly decreased compared with control. Expression of eNOS in the mesenteric vascular endothelium was modulated at 24 and 96 hpi. PAI-1 expression increased 3.47-fold at 96 hpi, while the concentration of PAI-1 in the blood plasma increased 6.43-fold at 24 hpi compared with control. The tPA concentration in plasma was also modulated at 24 hpi and 96 hpi. The obtained data indicate that influenza A(H1N1)pdm09 virus aggravates the course of premorbid acute cardiomyopathy in Wistar rats, causing pronounced dysregulation of endothelial factor expression and vasomotor activity impairment of mesenteric arteries.
流感病毒可感染血管内皮细胞，导致内皮功能障碍。患有急性和慢性心血管疾病的人是患严重流感的高危人群；然而，流感引起心血管系统改变的机制仍不完全清楚。本研究旨在评估感染甲型 H1N1pdm09 流感病毒的预先存在急性心肌病变的 Wistar 大鼠肠系膜血管的功能活性。为此，我们使用线描记法测定了（1）Wistar 大鼠肠系膜血管的血管舒缩活性，（2）肠系膜血管内皮中三种内皮因子的表达水平：内皮型一氧化氮合酶（eNOS）、纤溶酶原激活物抑制剂-1（PAI-1）和组织型纤溶酶原激活物（tPA），使用免疫组织化学，（3）使用 ELISA 测定血浆中的 PAI-1 和 tPA 浓度。动物的急性心肌病是通过阿霉素（DOX）感染大鼠适应的甲型 H1N1pdm09 病毒后诱导的。在感染后 24 和 96 小时（hpi）分析肠系膜血管的功能活性。因此，与对照组相比，肠系膜动脉对血管收缩剂和血管扩张剂的最大反应在 24 和 96 hpi 时显著降低。肠系膜血管内皮中 eNOS 的表达在 24 和 96 hpi 时受到调节。PAI-1 的表达在 96 hpi 时增加了 3.47 倍，而血浆中 PAI-1 的浓度在 24 hpi 时增加了 6.43 倍，与对照组相比。血浆中的 tPA 浓度也在 24 hpi 和 96 hpi 时受到调节。获得的数据表明，甲型 H1N1pdm09 病毒加重了 Wistar 大鼠预先存在的急性心肌病变的病程，导致内皮因子表达明显失调和肠系膜动脉的血管舒缩活性受损。
