PAH commonly defined by an elevated PAP (>25 mmHg at rest) and a normal pulmonary arterial wedge pressure (<15 mmHg), is characterized by a pre-capillary arteriopathy with the presence of vascular remodeling and formation of plexiform lesions, an increased pulmonary vascular resistance (PVR), which may result in right heart failure. PAH may be idiopathic (IPAH), heritable (HPAH) or associated with drug/toxin exposure or other medical conditions including connective tissue diseases, congenital heart diseases, human immunodeficiency virus or portal hypertension. Familial cases were already reported in the early fifties and, in 2000, bone morphogenic protein receptor type 2 gene (BMPR2) was identified as the gene responsible for more than 70% of HPAH and about 20% of IPAH. BMPR2 belongs to a superfamily of growth factor receptors, including bone morphogenic protein (BMPs) and transforming growth factor beta (TGF-β) and consequently controls cellular functions such as proliferation, migration, differentiation or apoptosis. BMPR2 mutations may favor activation of p38MAPK-dependent pro-proliferative pathways, which is also ; a key player in cytokine-induced inflammatory signaling pathways. Although BMPR2 mutation carriers develop PAH 10 years earlier than non-carriers and display more severe hemodynamic changes, only 20% of BMPR2 mutation carriers will further develop PAH. A role of inflammation in the pathogenesis of PAH has been suggested. A predictive role of various cytokines has been recently evidenced in PAH. The investigators have observed elevated C-reactive protein (CRP) circulating levels in PAH and evidenced a predictive role of CRP in PAH. Interestingly, heterozygous null BMPR2 mice failed to develop PAH unless an additional inflammatory insult was applied. More recently, inhibition of leukocyte recruitment has been shown to impair PAH progression in mice with genetic ablation of endothelial BMPR-II. This consequently suggests that inflammation could play the role of a second hit in BMPR2 mutation carriers to further develop PAH.