Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. PAH is divided into disease subgroups that include heritable (HPAH, formerly familial PAH), idiopathic (IPAH), and PAH associated with a variety of other systemic diseases or drug/toxin exposures. It has been discovered that altered BMPR2 signaling is the major heritable risk factor for development of PAH, via rare variants (mutations) in the BMPR2 gene (coding for a type II receptor member of the transforming growth factor [TGF]-beta family). Pathogenic mutations in the type I receptor ACVRL1 and, at a significantly lower frequency, the type III receptor endoglin in multiple kindreds cause PAH associated with hereditary hemorrhagic telangiectasia (HHT). Together, these observations support a prominent role for TGF-beta family members in the development of PAH.
Ma L, Roman-Campos D, Austin ED, Eyries M, Sampson KS, Soubrier F, Germain M, Tregouet DA, Borczuk A, Rosenzweig EB, Girerd B, Montani D, Humbert M, Loyd JE, Kass RS, Chung WK
タイトル
A novel channelopathy in pulmonary arterial hypertension.
Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L
タイトル
Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.
Eyries M, Montani D, Girerd B, Perret C, Leroy A, Lonjou C, Chelghoum N, Coulet F, Bonnet D, Dorfmuller P, Fadel E, Sitbon O, Simonneau G, Tregouet DA, Humbert M, Soubrier F
タイトル
EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension.
