Endothelial plasticity across PTEN and Hippo pathways: A complex hormetic rheostat modulated by extracellular vesicles.

Vascularization is a multifactorial and spatiotemporally regulated process, essential for cell and tissue survival. Vascular alterations have repercussions on the development and progression of diseases such as cancer, cardiovascular diseases, and diabetes, which are the leading causes of death worldwide. Additionally, vascularization continues to be a challenge for tissue engineering and regenerative medicine. Hence, vascularization is the center of interest for physiology, pathophysiology, and therapeutic processes. Within vascularization, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Hippo signaling have pivotal roles in the development and homeostasis of the vascular system. Their suppression is related to several pathologies, including developmental defects and cancer. Non-coding RNAs (ncRNAs) are among the regulators of PTEN and/or Hippo pathways during development and disease. The purpose of this paper is to review and discuss the mechanisms by which exosome-derived ncRNAs modulate endothelial cell plasticity during physiological and pathological angiogenesis, through the regulation of PTEN and Hippo pathways, aiming to establish new perspectives on cellular communication during tumoral and regenerative vascularization.

Dengue virus potentially promotes migratory responses on endothelial cells by enhancing pro-migratory soluble factors and miRNAs.

The most life-threatening effect of the Dengue virus (DENV) infection is an acute destabilization of the microvascular endothelial cell (MEC) barrier leading to plasma leakage, hypovolemic shock and haemorrhage. However, the underlying cellular mechanisms responsible for the dysfunction of MECs are not well understood. To identify potential cellular processes altered during DENV infection of MECs, expression profiles of cytokines/growth factors and microRNAs were measured by Luminex assay and next generation sequencing, respectively. Synchronously DENV2-infected MECs increase the secretion of IL-6, IL-8, FGF-2, GM-CSF, G-CSF, TGF-α, GRO, RANTES, MCP-1 and MCP-3. Conditioned media of infected MECs increased the migration of non-infected MECs. Furthermore, six miRNAs deregulated at 24 hpi were predicted to regulate host genes involved in cell migration and vascular developmental processes such as angiogenesis. These in silico analyses provide insights that support that DENV promotes an acute migratory phenotype in MECs that contributes to the vascular destabilization observed in severe dengue cases.