Decitabine Reactivation of FoxM1-Dependent Endothelial Regeneration and Vascular Repair for Potential Treatment of Elderly ARDS and COVID-19 Patients
Year: 2021
Type: preprint
Abstract: Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS) and COVID-19. We repot that aging impairs the intrinsic FoxM1-dependent endothelial regeneration and vascular repair program and causes persistent lung injury and high mortality following sepsis. Therapeutic gene transduction of FOXM1 in vascular endothelium or treatment with FDA-approved drug Decitabine was sufficient to reactivate FoxM1-dependent lung endothelial regeneration in aged mice, reverse aging-impaired resolution of inflammatory injury, and promote survival. In COVID-19 lung autopsy samples, FOXM1 expression was not induced in vascular endothelial cells of elderly patients in contrast to mid-age patients. Thus, Decitabine reactivation of FoxM1-dependent vascular repair represents a potential effective therapy for elderly COVID-19 and non-COVID-19 ARDS patients.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Novel mechanisms of obliterative pulmonary vascular remodeling and severe pulmonary arterial hypertension, Targeting Smooth Muscle Progenitor Cells for Treatment of Pulmonary Arterial Hypertension, Novel mechanisms of endothelial Injury in the pathogenesis of ARDS, Novel Signalings and Molecular Targets Of Endothelial Regeneration In Aging Lung
OpenAlex ID: W3158115326