miR-573 rescues endothelial dysfunction during dengue infection under PPARγ regulation.

Early prognosis of abnormal vasculopathy is essential for effective clinical management of severe dengue patients. An exaggerated interferon (IFN) response and release of vasoactive factors from endothelial cells cause vasculopathy. This study shows that dengue 2 (DENV2) infection of human umbilical vein endothelial cells (HUVEC) results in differentially regulated miRNAs important for endothelial function. miR-573 was significantly down-regulated in DENV2-infected HUVEC due to decreased Peroxisome Proliferator Activator Receptor Gamma (PPARγ) activity. Restoring miR-573 expression decreased endothelial permeability by suppressing the expression of vasoactive angiopoietin 2 (ANGPT2). We also found that miR-573 suppressed the proinflammatory IFN response through direct downregulation of toll like receptor 2 (TLR2) expression. Our study provides a novel insight into miR-573 mediated regulation of endothelial function during DENV2 infection which can be further translated into a potential therapeutic and prognostic agent for severe dengue patients. IMPORTANCE: We need to identify molecular factors which can predict the onset of endothelial dysfunction in dengue patients. Increase in endothelial permeability during severe dengue infections is poorly understood. In this study we focus on factors which regulate endothelial function and are dysregulated during DENV2 infection. We show that miR-573 rescues endothelial permeability and is downregulated during DENV2 infection in endothelial cells. This finding can have diagnostic as well as therapeutic applications.