Combination use of sildenafil and simvastatin increases BMPR-II signal transduction in rats with monocrotaline-mediated pulmonary hypertension

111 Dysfunctional bone morphogenetic protein (BMP) signaling has been found in patients with pulmonary arterial hypertension (PAH); however, the exact role of BMP signaling in the treatment of PAH remains unknown. The BMP receptor type II (BMPR-II) is a member of the TGF-β family of signaling molecules. Functional receptors are heterodimers composed of a BMPR-II subunit and a serine–threonine kinase type I subunit, of which there are three members: BMPR-Ia, BMPR-Ib and Alk2.[1,2] Both BMPR-II and BMPR-Ia/Ib are highly expressed in the pulmonary vascular smooth muscle and endothelium. The discovery of heterozygous mutations of the BMPR-II gene (BMPR2) in patients with hereditary (or familial) PAH and patients with idiopathic PAH [3,4] represented a significant advance in the understanding of the genetic contributions to PAH.