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Review
. 2018 Oct 17;19(10):3203.
doi: 10.3390/ijms19103203.

Pulmonary Arterial Hypertension and Hereditary Haemorrhagic Telangiectasia

Veronique M M Vorselaars  1 , Anna E Hosman  2 , Cornelis J J Westermann  3 , Repke J Snijder  4 , Johannes J Mager  5 , Marie-Jose Goumans  6 , Marco C Post  7
Affiliations
Review

Pulmonary Arterial Hypertension and Hereditary Haemorrhagic Telangiectasia

Veronique M M Vorselaars et al. Int J Mol Sci. .

Abstract

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterised by multisystemic vascular dysplasia. Heritable pulmonary arterial hypertension (HPAH) is a rare but severe complication of HHT. Both diseases can be the result of genetic mutations in ACVLR1 and ENG encoding for proteins involved in the transforming growth factor-beta (TGF-β) superfamily, a signalling pathway that is essential for angiogenesis. Changes within this pathway can lead to both the proliferative vasculopathy of HPAH and arteriovenous malformations seen in HHT. Clinical signs of the disease combination may not be specific but early diagnosis is important for appropriate treatment. This review describes the molecular mechanism and management of HPAH and HHT.

Keywords: ACVRL1; ENG; hereditary haemorrhagic telangiectasia; pulmonary arterial hypertension; pulmonary hypertension.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic diagram illustrating the transforming growth factor-beta (TGF-β) pathway and the genes and proteins involved in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). Illustrated are two pathways of ALK5/SMAD2-3 and ALK1/SMAD1-5. SMC, smooth muscle cell. P, phosphorylation.
Figure 2
Figure 2
Flow chart diagnosis of PH in HHT. HHT, hereditary haemorrhagic telangiectasia; PH, pulmonary hypertension; RHC, right heart catheterisation; PAH, pulmonary arterial hypertension.
Figure 3
Figure 3
Diagnosis of HHT in HPAH. HPAH, heritable pulmonary arterial hypertension; AVMs, arteriovenous malformations.
See this image and copyright information in PMC

References

    1. Galie N., Humbert M., Vachiery J.L., Gibbs S., Lang I., Torbicki A., Simonneau G., Peacock A., Vonk Noordegraaf A., Beghetti M., et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT) Eur. Heart J. 2016;37:67–119. - PubMed
    1. Soubrier F., Chung W.K., Machado R., Grunig E., Aldred M., Geraci M., Loyd J.E., Elliott C.G., Trembath R.C., Newman J.H., et al. Genetics and genomics of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2013;62:D13–D21. doi: 10.1016/j.jacc.2013.10.035. - DOI - PubMed
    1. Larkin E.K., Newman J.H., Austin E.D., Hemnes A.R., Wheeler L., Robbins I.M., West J.D., Phillips J.A., III, Hamid R., Loyd J.E. Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2012;186:892–896. doi: 10.1164/rccm.201205-0886OC. - DOI - PMC - PubMed
    1. Graf S., Haimel M., Bleda M., Hadinnapola C., Southgate L., Li W., Hodgson J., Liu B., Salmon R.M., Southwood M., et al. Identification of rare sequence variation underlying heritable pulmonary arterial hypertension. Nat. Commun. 2018;9 doi: 10.1038/s41467-018-03672-4. - DOI - PMC - PubMed
    1. Tillet E., Bailly S. Emerging roles of BMP9 and BMP10 in hereditary hemorrhagic telangiectasia. Front. Genet. 2015;5:456. doi: 10.3389/fgene.2014.00456. - DOI - PMC - PubMed

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