Dysregulated Bone Morphogenetic Protein Signaling in Monocrotaline-Induced Pulmonary Arterial Hypertension

• DOI: 10.1161/atvbaha.107.141200
• Publication Date: 2007-03-09T02:15:37Z
• Authors: Rory E. Morty; Bozena Nejman; Grazyna Kwapiszewska; Matthias Hecker; Anka Zakrzewicz; Fotini M. Kouri; Dorothea M. Peters; Rio Dumitrascu; Werner Seeger; Petra Knaus; Ralph T. Schermuly; Oliver Eickelberg
• Keywords: BMPR2

Mutations in the bmpr2 gene, encoding type II bone morphogenetic protein (BMP) receptor, have been identified patients with pulmonary arterial hypertension (PAH), implicating BMP signaling PAH. The aim of this study was to assess and its physiological effects a monocrotaline (MCT) model PAH.Expression receptors Ib II, Smads 4, 5, 6, 8, downregulated lungs but not kidneys MCT-treated rats. Smad1 phosphorylation expression BMP/Smad target genes id1 id3 also reduced, although ERK1/2 p38(MAPK) remained unaffected. receptor Smad expression, phosphorylation, induction BMP/Smad-responsive element promoter were reduced artery smooth muscle cells (PASMCs) from As consequence impaired signaling, PASMCs rats resistant apoptosis induced by BMP-4 BMP-7, antagonism proliferation platelet-derived growth factor.BMP BMP-regulated phenomena are perturbed rats, lending solid support proposed roles for pathogenesis human