IMPAIRED VASCULAR ENDOTHELIUM FUNCTIONAL PROPERTIES DURING THE ACUTE PHASE OF INFLUENZA A(H3N2) VIRUS-INDUCED INFECTION



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Abstract

Seasonal influenza A viruses including A(H1N1)pdm09 and A(H3N2) subtypes infect over 10-12% of the global population annually. According to epidemiological data, influenza A(H3N2) viruses are associated with more severe disease progression and the development of hemorrhagic syndrome as well as different thrombotic complications associated with activated vascular endothelial cells. Aim of the study. To investigate the effect of influenza A(H3N2) virus on the morphofunctional properties of blood vessel endothelium during the acute phase of infection. Materials and Methods. Wistar rats were intranasally infected with influenza A virus A/Port Chalmers/1/1973 (H3N2) in a volume of 0.1 ml and subsequently euthanized at 1- and 4-days post infection (d.p.i.) (n=5). Animals in control group were intranasally administered DMEM medium (0.1 ml). After necropsy, lung and mesentery tissues were collected to assess viral infectious activity titer. Additionally, severity of histopathological alterations in lung blood vessel endothelium and mesentery was assessed, the expression level of endothelial nitric oxide synthase (eNOS) in pulmonary and mesentery vascular endothelium was measured by immunohistochemical analysis, and the parameters of vasomotor activity in mesenteric arteries using wire myography was assessed. Results. Influenza A(H3N2) virus induced morphological changes in lung blood vessels on days 1 and 4, decreased eNOS expression levels in lung vessel endothelium at 1 d.p.i., and in mesenteric blood vessel endothelium at 1 and 4 d.p.i. Furthermore, the response of mesenteric blood vessels to median phenylephrine concentrations on day 4 vs. day 1 d.p.i. was 87.13% higher (p<0.05), while the vascular response to premaximal acetylcholine concentrations on day 4 was 26.15% lower (p<0.05) compared to control. Conclusion. Influenza A virus subtype H3N2 impairs the morphofunctional properties of the blood vessel endothelium in rat lungs and the functional properties of the vascular endothelium in the mesentery during the acute phase of infection, suggesting activation of endothelial cells at both local and systemic levels.

About the authors

Vladimir Marchenko

North-Western State Medical University Named after I.I. Mechnikov, St. Petersburg, Russian Federation

Email: vmarcenco@mail.ru
ORCID iD: 0000-0001-6870-3157
SPIN-code: 4463-7720
Scopus Author ID: 57218869259

Ph. D., assoc. prof. of Medical Microbiology Department

Russian Federation, 191015, Russia, St. Petersburg, Kirochnaya st., 41.

Irina Zelinskaya

V.A. Almazov National Medical Research Centre, Russian Ministry of Health, St. Petersburg, Russian Federation

Email: irina.selinskaja@gmail.com
ORCID iD: 0000-0002-1971-3444

Researcher of Laboratory of Bioprosthetics and Cardiac Protection, Institute of Experimental Medicine

Russian Federation, 197341 St. Petersburg, Russian Federation, Akkuratov st., 2.

Darya Mukhametdinova

V.A. Almazov National Medical Research Centre, Russian Ministry of Health, St. Petersburg, Russian Federation

Email: mukh.dv@yandex.ru
ORCID iD: 0000-0002-7109-1187

Research Assistant of Experimental Pathomorphology Group, Institute of Experimental Medicine

Russian Federation, 197341 St. Petersburg, Russian Federation, Akkuratov st., 2.

Yana Toropova

V.A. Almazov National Medical Research Centre, Russian Ministry of Health, St. Petersburg, Russian Federation

Email: yana.toropova@mail.ru
ORCID iD: 0000-0003-1629-7868

Sc. D., Head of Laboratory of Bioprosthetics and Cardiac Protection, Institute of Experimental Medicine

Russian Federation, 197341 St. Petersburg, Russian Federation, Akkuratov st., 2.

Michael Galagudza

V.A. Almazov National Medical Research Centre, Russian Ministry of Health, St. Petersburg, Russian Federation

Email: galagoudza@mail.ru
ORCID iD: 0000-0001-5129-9944

MD, Sc. D., Professor and Corresponding member of the Russian Academy of Sciences, Director of the Institute of Experimental Medicine of Almazov National Medical Research Institute, Saint Petersburg

Russian Federation, 197341 St. Petersburg, Russian Federation, Akkuratov st., 2.

Irirna Zhilinskaya

North-Western State Medical University Named after I.I. Mechnikov, St. Petersburg, Russian Federation

Author for correspondence.
Email: s_zhilinskaya@mail.ru
ORCID iD: 0000-0002-0084-1323

Sc. D., Professor of Medical Microbiology Department

Russian Federation, 191015, Russia, St. Petersburg, Kirochnaya st., 41.

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