COVID-19 Causes Ferroptosis and Oxidative Stress in Human Endothelial Cells.

Oxidative stress and endothelial dysfunction have been shown to play crucial roles in the pathophysiology of COVID-19 (coronavirus disease 2019). On these grounds, we sought to investigate the impact of COVID-19 on lipid peroxidation and ferroptosis in human endothelial cells. We hypothesized that oxidative stress and lipid peroxidation induced by COVID-19 in endothelial cells could be linked to the disease outcome. Thus, we collected serum from COVID-19 patients on hospital admission, and we incubated these sera with human endothelial cells, comparing the effects on the generation of reactive oxygen species (ROS) and lipid peroxidation between patients who survived and patients who did not survive. We found that the serum from non-survivors significantly increased lipid peroxidation. Moreover, serum from non-survivors markedly regulated the expression levels of the main markers of ferroptosis, including GPX4, SLC7A11, FTH1, and SAT1, a response that was rescued by silencing TNFR1 on endothelial cells. Taken together, our data indicate that serum from patients who did not survive COVID-19 triggers lipid peroxidation in human endothelial cells.

miR-142 Targets TIM-1 in Human Endothelial Cells: Potential Implications for Stroke, COVID-19, Zika, Ebola, Dengue, and Other Viral Infections.

T-cell immunoglobulin and mucin domain 1 (TIM-1) has been recently identified as one of the factors involved in the internalization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells, in addition to angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), neuropilin-1, and others. We hypothesized that specific microRNAs could target TIM-1, with potential implications for the management of patients suffering from coronavirus disease 2019 (COVID-19). By combining bioinformatic analyses and functional assays, we identified miR-142 as a specific regulator of TIM-1 transcription. Since TIM-1 has been implicated in the regulation of endothelial function at the level of the blood-brain barrier (BBB) and its levels have been shown to be associated with stroke and cerebral ischemia-reperfusion injury, we validated miR-142 as a functional modulator of TIM-1 in human brain microvascular endothelial cells (hBMECs). Taken together, our results indicate that miR-142 targets TIM-1, representing a novel strategy against cerebrovascular disorders, as well as systemic complications of SARS-CoV-2 and other viral infections.