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Original Research: PULMONARY VASCULAR DISEASE |

Mast Cell Inhibition Improves Pulmonary Vascular Remodeling in Pulmonary HypertensionMast Cells in Pulmonary Arterial Hypertension

Beatrijs Bartelds, MD, PhD; Rosa Laura E. van Loon, MD, PhD; Saffloer Mohaupt, BSc; Hans Wijnberg, BSc; Michael G. Dickinson, MD; Bibiche Boersma, BSc; Janny Takens, BSc; Mirjam van Albada, MD, PhD; Rolf M. F. Berger, MD, PhD
Author and Funding Information

From the Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, The Netherlands.

Correspondence to: Beatrijs Bartelds, MD, PhD, Center for Congenital Heart Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, Rm W4.189, CA 41, PO Box 30 001, 9700 RB Groningen, The Netherlands; e-mail: b.bartelds@umcg.nl


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(3):651-660. doi:10.1378/chest.11-0663
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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 PAH 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 PAH 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 PAH 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.

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