Figure 1: Vascular remodeling diseases are characterized by an inappropriate inward narrowing of the vessels that obstruct the lumen and decrease the flow. In artherosclerosis, there is an important role of “bad cholesterol” low-density lipoprotein (LDL) that once oxidized, is incorporated by leucocytes (monocytes, lymphocytes…) to form foam cells that and accumulate in the sub-endothelial space due to an impaired migration. Vascular smooth muscle cells (VSMCs) migrate into the neointima and secrete matrix proteins to stabilize the plaque. Instability in the cap may lead to rupture and subsequent thrombus formation. In hyperplasia and pulmonary arterial hypertension, the narrowing is due to increased VSMCs constriction, proliferation and survival, fulfilling the internal space. Pro-inflammatory molecules, vasoconstrictors and growth factors play a critical role in the enhancement of this inappropriate VSMCs phenotype. Dehydroepiandrosterone (DHEA), that has been described to have anticholesterol, anti-proliferative, anti-inflammatory and vasodilating properties appear to be beneficial in the treatment of vascular remodeling diseases. Nonetheless, the exact mechanism by which DHEA acts is still unclear. Several evidences suggest that DHEA is a peroxisome proliferator. Through PPAR factors activation, several genes implicated in lipid metabolism are expressed, dereasing LDL accumulation. PPARα is also implicated in inhibition of inflammation by antagonize NF-κB. Moreover PPAR factors are able to enhance the expression of genes like glutaredoxin (GRX1), playing an important role in the downregulation of tyrosine phosphorylation, like for the PDGF receptor, and glutathionylation, a post transcriptional modification that could be implicated in DHEA-dependant inhibition of signaling factors such as Akt, STAT3 and NF-κB. Originally, DHEA was described as an inhibitor of the glucose 6-phosphate deshydrogenase (G6PDH), whose role in vascular remodeling processes is unknown. However, G6PDH inhibition is known to change NADPH ratio, whose reduced levels lead to decreased fatty acid production and subsequent reduction of LDL production; GSH ratio, which is also implicated in protein glutathionylation; and reactive oxygen species (ROS) production implicated in enhanced vasdilatation. Thus, DHEA-dependant G6PDH inhibition could also be beneficial in the treatment of vascular remodeling diseases.