PDGF signaling in pulmonary arterial hypertension.
The pathobiology of pulmonary arterial hypertension (PAH) includes endothelial cell dysfunction and proliferation and migration of VSMCs. As PDGF has been implicated in these processes, Schermuly et al. hypothesized that altered PDGF signaling may be involved in the vascular remodeling observed in PAH. To explore this notion further, the authors evaluated the effects of the PDGF receptor inhibitor STI571 in 2 different animal models of pulmonary hypertension. In both models, after development of pulmonary vascular disease, administration of STI571 reversed pulmonary vascular changes. These studies provide preclinical proof of concept for the clinical development of a PDGF inhibitor as a targeted therapy for PAH patients.
Barst
Robyn J
RJ
New York Presbyterian Pulmonary Hypertension Center, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA. rjb3@columbia.edu
D000818:Animals; D001549:Benzamides; D004195:Disease Models, Animal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism*; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011651:Pulmonary Artery / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism
D001549:Benzamides; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor