Because PAI-1 promoter has cortisol and insulin response, depressed individuals may have elevated levels of PAI-1 activity, even after adjusting for confounders, such as coronary heart disease, smoking, hypertension, triglyceride concentration, and body mass index.16 Also, serotonin has been shown to increase PAI-1 levels in endothelial cells.17 This evidence concerns the gene SERPINE1 and hypertensive disorder.