Mast Cell Inhibition Improves Pulmonary Vascular Remodeling in Pulmonary Hypertension

Beatrijs Bartelds*, Rosa Laura E. van Loon, Saffloer Mohaupt, Hans Wijnberg, Michael G. Dickinson, Janny Takens, Mirjam van Albada, Rolf M. F. Berger, B. Boersma

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

37 Citations (Scopus)

Abstract

Background: Pulmonary arterial hypertension (PAH) is a progressive angioproliferative disease with high morbidity and mortality. Although the histopathology is well described, its pathogenesis is largely unknown. We previously identified the increased presence of mast cells and their markers in a rat model of flow-associated PAH. The aim of this study was to test the effect of mast cell stabilization on pulmonary vascular remodeling in experimental PAH.

Methods: Rats with flow-associated PAR created by monocrotaline and an aorto-caval shunt were treated with the mast cell stabilizer cromolyn and compared with untreated rats and control rats. Further, we treated a group of rats with PAR with an inhibitor (TY-51469) of chymase, one of the mast cell proteases. The effects on pulmonary vascular remodeling and hemodynamics were assessed.

Results: Rats with PAR had increased mast cells, chymase activity, and inflammatory markers. Treatment with mast cell stabilizer attenuated pulmonary vascular remodeling but not hemodynamics. A lower pulmonary chymase activity correlated with more favorable pulmonary vascular remodeling as well as hemodynamics and inflammatory markers.

Conclusions: We showed in rats with PAH that mast cell stabilization attenuated pulmonary vascular remodeling and that a lower chymase activity correlated with more favorable hemodynamics and pulmonary vascular remodeling. The results of this experimental study support the concept of the use of antiinflammatory therapy by mast cell stabilizers, a group of drugs already licensed for clinical use, to attenuate disease progression in PAH. CHEST 2012; 141(3):651-660

Original languageEnglish
Pages (from-to)651-660
Number of pages10
JournalChest
Volume141
Issue number3
DOIs
Publication statusPublished - Mar-2012

Keywords

  • ARTERIAL-HYPERTENSION
  • EISENMENGER-SYNDROME
  • ANIMAL-MODELS
  • DOUBLE-BLIND
  • CHYMASE
  • RATS
  • STABILIZATION
  • TREPROSTINIL
  • ANGIOGENESIS
  • INFLAMMATION

Cite this