KEGG   DISEASE: Pulmonary arterial hypertension
Entry
H01621                      Disease                                
Name
Pulmonary arterial hypertension
Description
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.
Category
Cardiovascular disease
Brite
Human diseases [BR:br08402]
 Cardiovascular diseases
  Hypertensive diseases
   H01621  Pulmonary arterial hypertension
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
Related
pathway
hsa04350  TGF-beta signaling pathway
Gene
(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]
Drug
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
Reference
  Authors
Lai YC, Potoka KC, Champion HC, Mora AL, Gladwin MT
  Title
Pulmonary arterial hypertension: the clinical syndrome.
  Journal
Circ Res 115:115-30 (2014)
DOI:10.1161/CIRCRESAHA.115.301146
Reference
  Authors
Soubrier F, Chung WK, Machado R, Grunig E, Aldred M, Geraci M, Loyd JE, Elliott CG, Trembath RC, Newman JH, Humbert M
  Title
Genetics and genomics of pulmonary arterial hypertension.
  Journal
J Am Coll Cardiol 62:D13-21 (2013)
DOI:10.1016/j.jacc.2013.10.035
Reference
  Authors
Austin ED, Loyd JE
  Title
The genetics of pulmonary arterial hypertension.
  Journal
Circ Res 115:189-202 (2014)
DOI:10.1161/CIRCRESAHA.115.303404
Reference
PMID:10973254 (BMPR2)
  Authors
Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC
  Title
Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension.
  Journal
Nat Genet 26:81-4 (2000)
DOI:10.1038/79226
Reference
PMID:19211612 (SMAD9)
  Authors
Shintani M, Yagi H, Nakayama T, Saji T, Matsuoka R
  Title
A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension.
  Journal
J Med Genet 46:331-7 (2009)
DOI:10.1136/jmg.2008.062703
Reference
PMID:22474227 (CAV1)
  Authors
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
  Title
Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension.
  Journal
Circ Cardiovasc Genet 5:336-43 (2012)
DOI:10.1161/CIRCGENETICS.111.961888
Reference
PMID:23883380 (KCNK3)
  Authors
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
  Title
A novel channelopathy in pulmonary arterial hypertension.
  Journal
N Engl J Med 369:351-361 (2013)
DOI:10.1056/NEJMoa1211097
Reference
PMID:30679663 (ATP13A3)
  Authors
Barozzi C, Galletti M, Tomasi L, De Fanti S, Palazzini M, Manes A, Sazzini M, Galie N
  Title
A Combined Targeted and Whole Exome Sequencing Approach Identified Novel Candidate Genes Involved in Heritable Pulmonary Arterial Hypertension.
  Journal
Sci Rep 9:753 (2019)
DOI:10.1038/s41598-018-37277-0
Reference
PMID:11484689 (ACVRL1)
  Authors
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
  Title
Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.
  Journal
N Engl J Med 345:325-34 (2001)
DOI:10.1056/NEJM200108023450503
Reference
PMID:24292273 (EIF2AK4)
  Authors
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
  Title
EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension.
  Journal
Nat Genet 46:65-9 (2014)
DOI:10.1038/ng.2844
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