Furthermore, several IGFBPs, particularly IGFBP-1, IGFBP-2, and IGFBP-3, are upregulated in PAH and may regulate IGF-1 bioavailability or exert IGF-independent actions that affect endothelial function and vascular homeostasis (Delafontaine et al., 2004). This evidence concerns the gene IGF1 and pulmonary arterial hypertension.