tacrolimus and Pulmonary-Arterial-Hypertension

Right ventricular (RV) function is the predominant determinant of survival in patients with pulmonary arterial hypertension (PAH). In preclinical models, pharmacological activation of BMP (bone morphogenetic protein) signaling with FK506 (tacrolimus) improved RV function by decreasing RV afterload. FK506 therapy further stabilized three patients with end-stage PAH. Whether FK506 has direct effects on the pressure-overloaded right ventricle is yet unknown. We hypothesized that increasing cardiac BMP signaling with FK506 improves RV structure and function in a model of fixed RV afterload after pulmonary artery banding (PAB). Direct cardiac effects of FK506 on the microvasculature and RV fibrosis were studied after surgical PAB in wild-type and heterozygous

Topics: Animals; Bone Morphogenetic Protein Receptors, Type II; Bone Morphogenetic Proteins; Fibroblasts; Fibrosis; Humans; Male; Mice; Mice, Mutant Strains; Myocardium; Pulmonary Arterial Hypertension; Signal Transduction; Tacrolimus; Ventricular Function, Right