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Physiologie, Klassifikation, Pathologie und Pathophysiologie

Das Wichtigste in aller Kürze

Physiology, classification, pathology and pathophysiology

The most important points very briefly

  • Leitthema
  • Published:
Der Pneumologe Aims and scope

Zusammenfassung

Die pulmonale Hypertonie (PH) ist eine komplexe Erkrankung mit verschiedenen Phänotypen. Ein Update der Klassifikation wurde 2013 bei der Weltkonferenz in Nizza erstellt und weist nur marginale Änderungen gegenüber Dana Point, 2008, auf. Auffällig ist eine deutliche Zunahme des medianen Alters der IPAH-Patienten bei Diagnosestellung. In der Zukunft ist zu erwarten, dass durch die zunehmende Alterung der Bevölkerung die Anzahl der Patienten mit verschiedenen Formen der PH deutlich steigen wird. Die Forschung im Bereich der Epigenetik und Genetik hat in den letzten Jahren viele Erkenntnisse mit großer Relevanz für die Diagnostik, Prognose und Therapie der PH hervorgebracht. Die aktuellen histopathologischen Untersuchungen sprechen gegen einen stadienhaften Verlauf der Krankheit. Diese Erkenntnisse könnten möglicherweise Grundlage für die Entwicklung neuer, personalisierter Therapiestrategien sein.

Abstract

Pulmonary hypertension (PH) is a complex disease with various phenotypes. During the PH World conference in Nice in 2013, an updated classification of PH was decided that included only minor modifications as compared to the previous classification from Dana Point in 2008. There has been an increase in the median age of idiopathic pulmonary arterial hypertension (IPAH) patients. With an aging population a significant increase in the incidence and prevalence of PH is expected. This increase is also based on improved diagnosis especially in elderly patients and on increased survival due to targeted therapies. In the field of pathophysiology and histopathology, significant advances have been made in recent years. The analysis of the molecular mechanisms and histopathology may help in understanding the disease mechanisms. The future challenge is how to use this knowledge for development of novel, perhaps personalized treatment strategies.

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Literatur

  1. Alastalo TP, Li M, Perez VJ et al (2011) Disruption of PPARgamma/beta-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. J Clin Invest 121:3735–3746

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Austin ED, Ma L, LeDuc C et al (2012) Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension. Circ Cardiovasc Genet 5:336–343

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Bertero T, Lu Y, Annis S et al (2014) Systems-level regulation of microRNA networks by miR-130/301 promotes pulmonary hypertension. J Clin Invest 124:3514–3528

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Biasin V, Marsh LM, Egemnazarov B et al (2014) Meprin beta, a novel mediator of vascular remodelling underlying pulmonary hypertension. J Pathol 233:7–17

    Article  CAS  PubMed  Google Scholar 

  5. Bjornsson J, Edwards WD (1985) Primary pulmonary hypertension: a histopathologic study of 80 cases. Mayo Clin Proc 60:16–25

    Article  CAS  PubMed  Google Scholar 

  6. Bogaard HJ, Mizuno S, Hussaini AA et al (2011) Suppression of histone deacetylases worsens right ventricular dysfunction after pulmonary artery banding in rats. Am J Respir Crit Care Med 183:1402–1410

    Article  CAS  PubMed  Google Scholar 

  7. Brock M, Samillan VJ, Trenkmann M et al (2012) AntagomiR directed against miR-20a restores functional BMPR2 signalling and prevents vascular remodelling in hypoxia-induced pulmonary hypertension. Eur Heart J 35(45):3203–3211

    Article  PubMed  Google Scholar 

  8. Chazova I, Loyd JE, Zhdanov VS et al (1995) Pulmonary artery adventitial changes and venous involvement in primary pulmonary hypertension. Am J Pathol 146:389–397

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Courboulin A, Paulin R, Giguère NJ et al (2011) Role for miR-204 in human pulmonary arterial hypertension. J Exp Med 208:535–548

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Deng Z, Morse JH, Slager SL et al (2000) Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 67:737–744

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Heath D, Edwards JE (1958) The pathology of hypertensive pulmonary vascular disease; a description of six grades of structural changes in the pulmonary arteries with special reference to congenital cardiac septal defects. Circulation 18:533–547

    Article  CAS  PubMed  Google Scholar 

  12. Hoeper MM, Huscher D, Ghofrani HA et al (2013) Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol 168:871–880

    Article  PubMed  Google Scholar 

  13. Hoffmann J, Wilhelm J, Marsh LM et al (2014) Distinct differences in gene expression patterns in pulmonary arteries of patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis with pulmonary hypertension. Am J Respir Crit Care Med 190:98–111

    Article  CAS  PubMed  Google Scholar 

  14. Kovacs G, Berghold A, Scheidl S, Olschewski H (2009) Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 34(4):888–894

    Article  CAS  PubMed  Google Scholar 

  15. Kwapiszewska G, Chwalek K, Marsh LM et al (2012) BDNF/TrkB signaling augments smooth muscle cell proliferation in pulmonary hypertension. Am J Pathol 181:2018–2029

    Article  CAS  PubMed  Google Scholar 

  16. Kwapiszewska G, Markart P, Dahal BK et al (2012) PAR-2 inhibition reverses experimental pulmonary hypertension. Circ Res 110(9):1179–1191

    Article  CAS  PubMed  Google Scholar 

  17. Li Y, Connolly M, Nagaraj C et al (2012) Peroxisome proliferator-activated receptor-beta/delta, the acute signaling factor in prostacyclin-induced pulmonary vasodilation. Am J Respir Cell Mol Biol 46:372–379

    Article  CAS  PubMed  Google Scholar 

  18. Ma L, Roman-Campos D, Austin ED et al (2013) A novel channelopathy in pulmonary arterial hypertension. N Engl J Med 369:351–361

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Olschewski A, Li Y, Tang B et al (2006) Impact of TASK-1 in human pulmonary artery smooth muscle cells. Circ Res 98:1072–1080

    Article  CAS  PubMed  Google Scholar 

  20. Olschewski A, Papp R, Nagaraj C, Olschewski H (2014) Ion channels and transporters as therapeutic targets in the pulmonary circulation. Pharmacol Ther 144(3):349–368

    Article  CAS  PubMed  Google Scholar 

  21. Overbeek MJ, Vonk MC, Boonstra A et al (2009) Pulmonary arterial hypertension in limited cutaneous systemic sclerosis: a distinctive vasculopathy. Eur Respir J 34:371–379

    Article  CAS  PubMed  Google Scholar 

  22. Pietra GG, Edwards WD, Kay JM et al (1989) Histopathology of primary pulmonary hypertension. a qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry. Circulation 80:1198–1206

    Article  CAS  PubMed  Google Scholar 

  23. Price LC, Wort SJ, Perros F et al (2012) Inflammation in pulmonary arterial hypertension. Chest 141:210–221

    Article  CAS  PubMed  Google Scholar 

  24. Pullamsetti SS, Doebele C, Fischer A et al (2012) Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension. Am J Respir Crit Care Med 185:409–419

    Article  CAS  PubMed  Google Scholar 

  25. Rabinovitch M (2012) Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 122:4306–4313

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Rabinovitch M, Haworth SG, Castaneda AR et al (1978) Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease. Circulation 58:1107–1122

    Article  CAS  PubMed  Google Scholar 

  27. Rhodes CJ, Wharton J, Boon RA et al (2013) Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension. Am J Respir Crit Care Med 187:294–302

    Article  CAS  PubMed  Google Scholar 

  28. Riley RL, Himmelstein A (1948) Studies of the pulmonary circulation at rest and during exercise in normal individuals and in patients with chronic pulmonary disease. Am J Physiol 152:372–382

    CAS  PubMed  Google Scholar 

  29. Saco TV, Parthasarathy PT, Cho Y et al (2014) Role of epigenetics in pulmonary hypertension. Am J Physiol Cell Physiol 306:C1101–C1105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Savai R, Al-Tamari HM, Sedding D et al (2014) Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension. Nat Med 20:1289–1300

    Article  CAS  PubMed  Google Scholar 

  31. Savai R, Pullamsetti SS, Kolbe J et al (2012) Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 186:897–908

    Article  CAS  PubMed  Google Scholar 

  32. Simonneau G, Gatzoulis MA, Adatia I et al (2013) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 62:D34–D41

    Article  PubMed  Google Scholar 

  33. Soubrier F, Chung WK, Machado R et al (2013) Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol 62:D13–D21

    Article  CAS  PubMed  Google Scholar 

  34. Stacher E, Graham BB, Hunt JM et al (2012) Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med 186:261–272

    Article  PubMed Central  PubMed  Google Scholar 

  35. Tabeling C, Yu H, Wang L et al (2015) CFTR and sphingolipids mediate hypoxic pulmonary vasoconstriction. Proc Natl Acad Sci U S A 112:E1614–E1623

    Article  CAS  PubMed  Google Scholar 

  36. Tang B, Li Y, Nagaraj C et al (2009) Endothelin-1 inhibits background two-pore domain channel TASK-1 in primary human pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol 41:476–483

    Article  CAS  PubMed  Google Scholar 

  37. Upton PD, Davies RJ, Tajsic T, Morrell NW (2013) Transforming growth factor-beta (1) represses bone morphogenetic protein-mediated Smad signaling in pulmonary artery smooth muscle cells via Smad3. Am J Respir Cell Mol Biol 49:1135–1145

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Euler US von, Liljestrand G (1946) Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 12:301–320

    Article  Google Scholar 

  39. Wagenvoort CA (1980) Lung biopsy specimens in the evaluation of pulmonary vascular disease. Chest 77:614–625

    Article  CAS  PubMed  Google Scholar 

  40. Wagenvoort CA, Wagenvoort N (1970) Primary pulmonary hypertension: a pathologic study of the lung vessels in 156 clinically diagnosed cases. Circulation 42:1163–1184

    Article  Google Scholar 

  41. Wang L, Yin J, Nickles HT et al (2012) Hypoxic pulmonary vasoconstriction requires connexin 40-mediated endothelial signal conduction. J Clin Invest 122:4218–4230

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Yamaki S, Wagenvoort CA (1985) Comparison of primary plexogenic arteriopathy in adults and children. a morphometric study in 40 patients. Br Heart J 54:428–434

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Yi ES, Kim H, Ahn H et al (2000) Distribution of obstructive intimal lesions and their cellular phenotypes in chronic pulmonary hypertension. a morphometric and immunohistochemical study. Am J Respir Crit Care Med 162:1577–1586

    Article  CAS  PubMed  Google Scholar 

  44. Zhao L, Chen CN, Hajji N et al (2012) Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid. Circulation 126:455–467

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. G. Kwapiszewska und E. Stacher geben an, dass kein Interessenkonflikt besteht.

A. Olschewski weist auf folgende Beziehungen hin: Honorare für Vorträge von Bayer.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Universitätsklinik für Anästhesiologie und Intensivmedizin, Medizinische Universität Graz, Graz, Österreich

    G. Kwapiszewska &  A. Olschewski

  2. Ludwig Boltzmann Institut für Lungengefäßforschung, Stiftingtalstr. 24, 8010, Graz, Österreich

    G. Kwapiszewska &  A. Olschewski

  3. Institut für Pathologie, Medizinische Universität Graz, Graz, Österreich

    E. Stacher

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  1. G. Kwapiszewska
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  2. E. Stacher
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  3. A. Olschewski
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Correspondence to A. Olschewski.

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Kwapiszewska, G., Stacher, E. & Olschewski, A. Physiologie, Klassifikation, Pathologie und Pathophysiologie. Pneumologe 12, 373–380 (2015). https://doi.org/10.1007/s10405-015-0879-z

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