Artículos de revistas
Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support
Fecha
2022Registro en:
Frontiers in Medicine March 2022 | Volume 9 | Article 826218
10.3389/fmed.2022.826218
Autor
Maldonado Caniulao, Felipe
Morales, Diego
Díaz Papapietro, Catalina
Valdés, Catalina
Fernández, Christián
Valls Jiménez, Nicolás
Lazo C., Marioli
Espinoza Zamorano, Carolina
González Cornejo, Roberto
Gutiérrez Rojas, Rodrigo
Jara Schnettler, Alvaro
Romero Patiño, Carlos
Cerda Arancibia, Oscar
Cáceres Lluch, Mónica
Institución
Resumen
Purpose: Endothelial damage and angiogenesis are fundamental elements of
neovascularisation and fibrosis observed in patients with coronavirus disease 2019
(COVID-19). Here, we aimed to evaluate whether early endothelial and angiogenic
biomarkers detection predicts mortality and major cardiovascular events in patients with
COVID-19 requiring respiratory support.
Methods: Changes in serum syndecan-1, thrombomodulin, and angiogenic factor
concentrations were analysed during the first 24 h and 10 days after COVID-19
hospitalisation in patients with high-flow nasal oxygen or mechanical ventilation. Also,
we performed an exploratory evaluation of the endothelial migration process induced by
COVID-19 in the patients’ serum using an endothelial cell culture model.
Results: In 43 patients, mean syndecan-1 concentration was 40.96 ± 106.9 ng/mL
with a 33.9% increase (49.96 ± 58.1 ng/mL) at day 10. Both increases were significant
compared to healthy controls (Kruskal–Wallis p < 0.0001). We observed an increase
in thrombomodulin, Angiopoietin-2, human vascular endothelial growth factor (VEGF),
and human hepatocyte growth factor (HGF) concentrations during the first 24 h, with
a decrease in human tissue inhibitor of metalloproteinases-2 (TIMP-2) that remained
after 10 days. An increase in human Interleukin-8 (IL-8) on the 10th day accompanied
by high HGF was also noted. The incidence of myocardial injury and pulmonary
thromboembolism was 55.8 and 20%, respectively. The incidence of in-hospital deaths
was 16.3%. Biomarkers showed differences in severity of COVID-19. Syndecan-1,
human platelet-derived growth factor (PDGF), VEGF, and Ang-2 predicted mortality. A
multiple logistic regression model with TIMP-2 and PDGF had positive and negative predictive powers of 80.9 and 70%, respectively, for mortality. None of the biomarkers
predicted myocardial injury or pulmonary thromboembolism. A proteome profiler array
found changes in concentration in a large number of biomarkers of angiogenesis and
chemoattractants. Finally, the serum samples from COVID-19 patients increased cell
migration compared to that from healthy individuals.
Conclusion: We observed that early endothelial and angiogenic biomarkers predicted
mortality in patients with COVID-19. Chemoattractants from patients with COVID-19
increase the migration of endothelial cells. Trials are needed for confirmation, as this
poses a therapeutic target for SARS-CoV-2.