PT  - JOURNAL ARTICLE
AU  - J. Hoffmann
AU  - J. Yin
AU  - M. Kukucka
AU  - N. Yin
AU  - I. Saarikko
AU  - A. Sterner-Kock
AU  - H. Fujii
AU  - H. Leong-Poi
AU  - H. Kuppe
AU  - R.T. Schermuly
AU  - W.M. Kuebler
TI  - Mast cells promote lung vascular remodeling in pulmonary hypertension
AID  - 10.1183/09031936.00043310
DP  - 2010 Jan 01
TA  - European Respiratory Journal
PG  - erj00433-2010
4099  - http://erj.ersjournals.com/content/early/2010/12/09/09031936.00043310.short
4100  - http://erj.ersjournals.com/content/early/2010/12/09/09031936.00043310.full
AB  - Left heart disease (LHD) frequently causes lung vascular remodeling and pulmonary hypertension (PH). Yet, pharmacological treatment for PH in LHD is lacking, and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD, and to test their relevance and therapeutic potential.In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western, and functional relevance was tested in vivo by genetic and pharmacological strategies.In lungs of LHD rats, “mast cell activation” was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels, and remodeled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabilizer ketotifen, or in mast cell deficient Ws/Ws rats, PH and vascular remodeling were largely attenuated. Both strategies also reduced PH and vascular remodeling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to non-cardiogenic PH.In PH of different etiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodeling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH.