INTRODUCTION: Through pro-inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), and by modulators of nuclear activity, such as nuclear factor kappa B (NF-κB), the cytokine storm generated by the respiratory virus SARS-CoV-2, responsible for the current pandemic, promotes a process of activation of alveolar vascular endothelium cells, triggering structural and metabolic changes in these cells. Hypoxia is one of the consequences of endothelial damage caused by systemic inflammatory response syndrome (SIRS), which is observed in severe infectious processes and widely used to describe the cytokine storm evidenced in COVID-19. When the cellular environment feels hypoxia, the transcriptional activity of hypoxia-induced alpha factor (HIF-1α) is induced, and when combined with the endothelial injury itself, its gives rise to the process of formation of new vessels by stimulating the activity of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF). OBJECTIVES: To evaluate the tissue immunohistochemical expression of HIF-1α, TNF-α, NF-κB, and VEGF in lung samples from patients who died from severe lung disease caused by the SARS-CoV-2 and H1N1 pandemic virus and lung samples from the control group – correlating HIF-1α expression with clinical data of mechanical ventilation time and length of hospital stay until death, to understand better the molecular pathway involved in the process of angiogenesis promoted by the virus. MATERIALS AND METHODS: This research included post-mortem lung samples in three groups: COVID-19 (n=24), H1N1 (n=10) and CONTROL group (n=11). We analyzed the tissue expression of the biomarker HIF-1α and its precursor (NF-KB) and pro-inflammatory and angiogenic factors, respectively, TNF-α and VEGF. Thus, we tried to correlate the expression of HIF-1α with the events of endothelial injury and angiogenesis. We also analyzed the histopathological pattern of the disease concerning endothelial activation and vascular hypertrophy. The applied techniques were immunohistochemistry, morphometry, and Hematoxylin-Eosin staining. We observed the clinical data of the patients and compared them with the groups using statistical tests. RESULTS: a significantly elevated tissue expression of HIF-1α was found, however similar in all groups according to their quantitative medians, resulting in a non-statistical significance between the tissue expression of HIF-1α with the analyzed groups (p = 0.64). We also noted that HIF1-α is more degraded in the longer contact time with the O2 of mechanical ventilation. FINAL CONSIDERATIONS: Our study suggested the possible involvement of the TNF-α / NF-κB / HIF-1α / VEGF pathway during the angiogenesis event promoted by SARS-CoV-2.
