4 Diff erential Efects of Exercise Training on Mofi lament Phosphorylation and Function in Stable and Progressive Pulmonary Hypertension

Background – We have previously demonstrated opposite e¡ ects of exercise training in stable and progressive pulmonary hypertension (PH). Here we investigated cellular changes which may underlie the opposite e¡ ects of exercise training by focusing on right ventricular myolament protein phosphorylation and function. Methods and results – Histological analyses revealed exercise training in progressive PH induced massive leukocyte (Pinteraction<0.01), granulocyte (Pinteraction<0.05) and macrophage (Pinteraction<0.05) in ltration only in the right ventricle. By ProQ diamond analyses, we observed that phosphorylation of the myo lament proteins myosin binding protein C (Pinteraction<0.01), troponin T (Pinteraction<0.05) and troponin I (Pinteraction<0.05) was increased by exercise in stable PH and reduced in progressive PH. In progressive PH, reduced protein phosphorylation was associated with increased protein phosphatase 1 (PP1) expression. Myo lament Ca2+-sensitivity was increased in progressive PH (p<0.001) and reduced (p<0.01) in stable PH. Exercise training increased maximal force in both stable (p<0.05) and progressive PH (P<0.01), while passive force was signi cantly elevated upon exercise in progressive PH (pinteraction<0.05). Conclusions – The bene cial e¡ ect of exercise training in stable PH was associated with increased myo lament protein phosphorylation and RV contractility, whereas in progressive PH exercise training induced severe myocarditis, increased PP1 expression, reduced myo lament protein phosphorylation and resulted in increased passive sti¡ ness. Ch ap te r 4 Myo lament phosphorylation and function in experimental PH 57