Fig. 3: Cell death regulation in the platelet proteome.

A PPI related to programmed cell death and the apoptotic process. Colors represent biological processes. Proteins in blue are exclusive to programmed cell death and apoptotic processes. Proteins in green and purple are shared with PPI platelet activation and PPI response to type I interferon, respectively. In red, caspases 3 (DEP) and caspases 4, 5 and 9 (EPs) were upregulated in the COVID-19 group. B Caspase-1 activation in platelets isolated from healthy volunteers (controls) and patients with severe COVID-19. C Caspase 3/7 activation in platelets isolated from controls and patients with severe COVID-19. D Caspase 9 activation in platelets isolated from controls and patients with severe COVID-19 (percentage of positive cells by flow cytometry). E Western blot analysis of caspase 4 and β-actin expression in platelets isolated from three control subjects and 11 patients with severe COVID-19; and graph demonstrating band densitometry. F Cell death was evidenced by phosphatidylserine exposure (Annexin V positive) and collapse of the mitochondrial membrane potential (TMRE negative) in platelets isolated from control and patients with severe COVID-19 (percentage of cells by flow cytometry). Representative dot plots are shown in (B) and (F). Boxes indicate the median and interquartile ranges, and whiskers indicate minimal and maximal values in each group. *p < 0.05 compared to control with severe COVID-19 (unpaired t test).