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Pulmonary arterial hypertension associated with impaired lysosomal endothelin-1 degradation

Published online by Cambridge University Press:  09 June 2014

Sabine Recla ,
Andreas Hahn  and
Christian Apitz
Sabine Recla
Affiliation:
Pediatric Heart Centre, Justus-Liebig-University, Giessen, Germany
Andreas Hahn
Affiliation:
Pediatric Neurology, Justus-Liebig-University, Giessen, Germany
Christian Apitz*
Affiliation:
Pediatric Heart Centre, Justus-Liebig-University, Giessen, Germany
*
Correspondence to: Dr C. Apitz, Pediatric Heart Centre, University of Giessen, Feulgenstr. 12, D- 35385 Giessen, Germany. Tel: +49-64198543400; Fax: +49 64198543469; E-mail: Capitz@aol.com
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Abstract

We report on a boy with severe pulmonary arterial hypertension associated with mucolipidosis, a rare lysosomal storage disorder. During diagnostic catheterisation, we found increased endothelin-1 levels, but normal big endothelin-1-levels (the precursor form of endothelin-1), which suggests impaired degradation of endothelin-1 rather than increased synthesis. As endothelin-1 degradation takes place in the lysosome, it appears likely that lysosomal dysfunction caused by the underlying disease contributes to the development of pulmonary arterial hypertension in this patient.

Keywords

Pulmonary hypertensionendothelinpaediatric cardiologylysosomal storage disorder
Type
Brief Reports
Information
Cardiology in the Young , Volume 25 , Issue 4 , April 2015 , pp. 773 - 776
Copyright
© Cambridge University Press 2014 

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References

1. Berger, RM, Beghetti, M, Humpl, T, et al. Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 2012; 379: 537–546.CrossRefGoogle ScholarPubMed
2. Barst, RJ, McGoon, MD, Elliott, CG, Foreman, AJ, Miller, DP, Ivy, DD. Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation 2012; 125: 113–122.Google Scholar
3. Galiè, N, Manes, A, Branzi, A. The endothelin system in pulmonary arterial hypertension. Cardiovasc Res 2004; 61: 227–237.Google Scholar
4. Giaid, A, Yanagisawa, M, Langleben, D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328: 1732–1739.Google Scholar
5. Ishak, M, Zambrano, EV, Bazzy-Asaad, A, Esquibies, AE. Unusual pulmonary findings in mucolipidosis II. Pediatr Pulmonol 2012; 47: 719–721.CrossRefGoogle ScholarPubMed
6. Kovacevic, A, Schranz, D, Meissner, T, Pillekamp, F, Schmidt, KG. Mucolipidosis II complicated by severe pulmonary hypertension. Mol Genet Metab 2011; 104: 192–193.Google Scholar
7. Deng, Y, Jeng, AY. Soluble endothelin degradation enzyme activities in various rat tissues. Biochem Cell Biol 1992; 70: 1385–1389.Google Scholar
8. Wang, J, Chiou, WJ, Gagne, GD, Wu-Wong, JR. Internalization of type-A endothelin receptor. J Cardiovasc Pharmacol 2000; 36 (Suppl 1): S61–S65.CrossRefGoogle ScholarPubMed
9. Paasche, JD, Attramadal, T, Sandberg, C, Johansen, HK, Attramadal, H. Mechanisms of endothelin receptor subtype-specific targeting to distinct intracellular trafficking pathways. J Biol Chem 2001; 276: 34041–34050.Google Scholar
10. Bermek, H, Peng, KC, Angelova, K, Ergul, A, Puett, D. Endothelin degradation by vascular smooth muscle cells. Regul Pept 1996; 66: 155–162.CrossRefGoogle ScholarPubMed
11. Itoh, K, Kase, R, Shimmoto, M, Satake, A, Sakuraba, H, Suzuki, Y. Protective protein as an endogenous endothelin degradation enzyme in human tissues. J Biol Chem 1995; 270: 515–518.Google Scholar