Journalartikel
Autorenliste: Schermuly, Ralph Theo; Pullamsetti, Soni Savai; Kwapiszewska, Grazyna; Dumitrascu, Rio; Tian, Xia; Weissmann, Norbert; Ghofrani, Hossein Ardeschir; Kaulen, Christina; Dunkern, Torsten; Schudt, Christian; Voswinckel, Robert; Zhou, Jiang; Samidurai, Arun; Klepetko, Walter; Paddenberg, Renate; Kummer, Wolfgang; Seeger, Werner; Grimminger, Friedrich
Jahr der Veröffentlichung: 2007
Seiten: 2331-2339
Zeitschrift: Circulation
Bandnummer: 115
Heftnummer: 17
ISSN: 0009-7322
eISSN: 1524-4539
DOI Link: https://doi.org/10.1161/CIRCULATIONAHA.106.676809
Verlag: Lippincott, Williams & Wilkins
Background - Pulmonary arterial hypertension (PAH) is a life-threatening disease, characterized by vascular smooth muscle cell hyperproliferation. The calcium/calmodulin-dependent phosphodiesterase 1 (PDE1) may play a major role in vascular smooth muscle cell proliferation. Methods and Results - We investigated the expression of PDE1 in explanted lungs from idiopathic PAH patients and animal models of PAH and undertook therapeutic intervention studies in the animal models. Strong upregulation of PDE1C in pulmonary arterial vessels in the idiopathic PAH lungs compared with healthy donor lungs was noted on the mRNA level by laser-assisted vessel microdissection and on the protein level by immunohistochemistry. In chronically hypoxic mouse lungs and lungs from monocrotaline-injected rats, PDE1A upregulation was detected in the structurally remodeled arterial muscular layer. Long-term infusion of the PDE1 inhibitor 8-methoxymethyl 3-isobutyl-1-methylxanthine in hypoxic mice and monocrotaline-injected rats with fully established pulmonary hypertension reversed the pulmonary artery pressure elevation, structural remodeling of the lung vasculature (nonmuscularized versus partially muscularized versus fully muscularized small pulmonary arteries), and right heart hypertrophy. Conclusions - Strong upregulation of the PDE1 family in pulmonary artery smooth muscle cells is noted in human idiopathic PAH lungs and lungs from animal models of PAH. Inhibition of PDE1 reverses structural lung vascular remodeling and right heart hypertrophy in 2 animal models. The PDE1 family may thus offer a new target for therapeutic intervention in pulmonary hypertension.
Abstract:
Zitierstile
Harvard-Zitierstil: Schermuly, R., Pullamsetti, S., Kwapiszewska, G., Dumitrascu, R., Tian, X., Weissmann, N., et al. (2007) Phosphodiesterase 1 upregulation in pulmonary arterial hypertension target for reverse-remodeling therapy, Circulation, 115(17), pp. 2331-2339. https://doi.org/10.1161/CIRCULATIONAHA.106.676809
APA-Zitierstil: Schermuly, R., Pullamsetti, S., Kwapiszewska, G., Dumitrascu, R., Tian, X., Weissmann, N., Ghofrani, H., Kaulen, C., Dunkern, T., Schudt, C., Voswinckel, R., Zhou, J., Samidurai, A., Klepetko, W., Paddenberg, R., Kummer, W., Seeger, W., & Grimminger, F. (2007). Phosphodiesterase 1 upregulation in pulmonary arterial hypertension target for reverse-remodeling therapy. Circulation. 115(17), 2331-2339. https://doi.org/10.1161/CIRCULATIONAHA.106.676809
Schlagwörter
CAMP; ERECTILE DYSFUNCTION; hypertension, pulmonary; INHALED ILOPROST; muscle, smooth; ORAL SILDENAFIL; pharmacology; phosphodiesterases; SMOOTH-MUSCLE-CELLS; VASODILATOR
