They found that 5-HT elevated S100A4/Mts1 mRNA levels and increased S100A4/Mts1 PA-SMC lysates and culture media, indicating a mechanistic link between the 5-HT pathway and S100A4/Mts1 in pulmonary hypertension.[59] Besides that, advanced glycation endproducts (RAGE) binding S100A4 released by activated leukocytes results in the generation of reactive oxygen species and further activation of NF-κB.[60] This leads to reduced bioavailability of the labile vasodilator nitric oxide, reducing its anti-inflammatory effects and possibly compromising control of vascular tone directly. This evidence concerns the gene S100A4 and pulmonary hypertension.