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, In the present study, to the best of our knowledge, we report for the first time increased pericyte coverage of distal pulmonary arteries in experimental (in chronic hypoxia and monocrotaline-induced pulmonary hypertension) and human (patients carrying or not a bone morphogenetic protein receptor 2 mutation) pulmonary arterial hypertension (PAH), an abnormality that is a potential source of smooth muscle-like cells involved in the PAH pulmonary vascular remodeling. We obtained evidence that dysfunctional endothelial cells from patients with idiopathic PAH, through an aberrant release of key growth factors and chemoattractants (ie, fibroblast growth factor-2 and interleukin-6), contribute to this vascular abnormality. In vitro, we found that exogenous or endothelial-derived fibroblast growth factor-2 and interleukin-6 enhance pulmonary pericyte migration and that fibroblast growth factor-2 is also a pericyte mitogen. In addition, we demonstrated, in human lungs from patients with PAH and in a murine model of pulmonary hypertension, that these pericytes can differentiate into smooth muscle-like cells, expressing contractile proteins. We also found that transforming growth factor-?1 is overactivated in pulmonary pericytes from patients with idiopathic PAH and promotes human pulmonary pericyte differentiation into contractile smooth muscle-like cells. We thus suspect that neutralization of fibroblast growth factor-2, interleukin-6, and transforming growth factor-?1 may prevent pericyte recruitment and differentiation in idiopathic and heritable PAH, CLINICAL PERSPECTIVE Pulmonary vascular remodeling, occurring mostly in the small to midsized pulmonary arterioles (<500 ?m), is a hallmark of most forms of pulmonary hypertension and frequently leads to progressive functional decline in patients despite treatment with currently available therapies