KEGG DISEASE: Pulmonary arterial hypertension

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 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

Pathway

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]
(PPH6) CAPNS1 [HSA:826] [KO:K08583]
(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]
Sotatercept [DR:D09670]
Macitentan and tadalafil [DR:D12963]
Sildenafil [DR:D08514]
Sildenafil citrate [DR:D02229]
Tadalafil [DR:D02008]
Nitric oxide [DR:D00074]

Other DBs

ICD-11:

MeSH:

OMIM:

178600 615342 615343 615344 265400 620777 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 (PPH1)

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 (PPH2)

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 (PPH3)

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 (PPH4)

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 (PPH5)

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:38230350 (PPH6)

Authors

Postma AV, Rapp CK, Knoflach K, Volk AE, Lemke JR, Ackermann M, Regamey N, Latzin P, Celant L, Jansen SMA, Bogaard HJ, Ilgun A, Alders M, van Spaendonck-Zwarts KY, Jonigk D, Klein C, Graf S, Kubisch C, Houweling AC, Griese M

Title

Biallelic variants in the calpain regulatory subunit CAPNS1 cause pulmonary arterial hypertension.

Journal

Genet Med Open 1:100811 (2023)
DOI:10.1016/j.gimo.2023.100811

Reference

PMID:11484689 (HHT2)

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 (PVOD2)

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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