KEGG   DISEASE: Pulmonary arterial hypertension
H01621                      Disease                                
Pulmonary arterial hypertension
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.
Cardiovascular disease
Human diseases in ICD-11 classification [BR:br08403]
 11 Diseases of the circulatory system
  Pulmonary heart disease or diseases of pulmonary circulation
   BB01  Pulmonary hypertension
    H01621  Pulmonary arterial hypertension
hsa04350  TGF-beta signaling pathway
(PPH1) BMPR2 [HSA:659] [KO:K04671]
(PPH2) SMAD9 [HSA:4093] [KO:K16791]
(PPH3) CAV1 [HSA:857] [KO:K06278]
(PPH4) KCNK3 [HSA:3777] [KO:K04914]
(PPH5) ATP13A3 [HSA:79572] [KO:K14951]
(HHT2) ACVRL1 [HSA:94] [KO:K13594]
(PVOD2) EIF2AK4 [HSA:440275] [KO:K16196]
Epoprostenol [DR:D00106]
Epoprostenol sodium [DR:D01337]
Iloprost [DR:D02721]
Treprostinil [DR:D06213]
Treprostinil diolamine [DR:D10430]
Selexipag [DR:D09994]
Bosentan [DR:D01227]
Ambrisentan [DR:D07077]
Macitentan [DR:D10135]
Riociguat [DR:D09572]
Sildenafil [DR:D08514]
Sildenafil citrate [DR:D02229]
Tadalafil [DR:D02008]
Nitric oxide [DR:D00074]
Other DBs
ICD-11: BB01.0
ICD-10: I27
MeSH: D065627
OMIM: 178600 615342 615343 615344 265400 600376 234810
Lai YC, Potoka KC, Champion HC, Mora AL, Gladwin MT
Pulmonary arterial hypertension: the clinical syndrome.
Circ Res 115:115-30 (2014)
Soubrier F, Chung WK, Machado R, Grunig E, Aldred M, Geraci M, Loyd JE, Elliott CG, Trembath RC, Newman JH, Humbert M
Genetics and genomics of pulmonary arterial hypertension.
J Am Coll Cardiol 62:D13-21 (2013)
Austin ED, Loyd JE
The genetics of pulmonary arterial hypertension.
Circ Res 115:189-202 (2014)
PMID:10973254 (BMPR2)
Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC
Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension.
Nat Genet 26:81-4 (2000)
PMID:19211612 (SMAD9)
Shintani M, Yagi H, Nakayama T, Saji T, Matsuoka R
A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension.
J Med Genet 46:331-7 (2009)
PMID:22474227 (CAV1)
Austin ED, Ma L, LeDuc C, Berman Rosenzweig E, Borczuk A, Phillips JA 3rd, Palomero T, Sumazin P, Kim HR, Talati MH, West J, Loyd JE, Chung WK
Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension.
Circ Cardiovasc Genet 5:336-43 (2012)
PMID:23883380 (KCNK3)
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
A novel channelopathy in pulmonary arterial hypertension.
N Engl J Med 369:351-361 (2013)
PMID:30679663 (ATP13A3)
Barozzi C, Galletti M, Tomasi L, De Fanti S, Palazzini M, Manes A, Sazzini M, Galie N
A Combined Targeted and Whole Exome Sequencing Approach Identified Novel Candidate Genes Involved in Heritable Pulmonary Arterial Hypertension.
Sci Rep 9:753 (2019)
PMID:11484689 (ACVRL1)
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
Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.
N Engl J Med 345:325-34 (2001)
PMID:24292273 (EIF2AK4)
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
EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension.
Nat Genet 46:65-9 (2014)

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