Date: 26 Dec 2009

PDGF Receptor and its Antagonists: Role in Treatment of PAH

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Abstract

Pulmonary Hypertension is a severe lung disease, which is characterized by vasoconstriction and remodelling of the vessel wall. Mostly addressing the increased vascular tone, prostacyclin and its analogues, endothelin-receptor antagonists and phosphodiesterase type 5 inhibitors have been approved for treatment of PAH and represent the current therapeutic options. Mechanistically, these vasodilators decrease pulmonary vascular resistance and reduce thereby shear stress, which is a strong proliferative stimulus per se. Beside the development of new vasodilators, current research focuses on the development of causal treatment regimens aiming a normalization of the vessel structure. Mechanistically, increased proliferation, migration and a resistance to apoptosis of vascular cells represent key events in disease progression. In this context, tyrosine kinase inhibitors like imatinib have been shown to possess reverse remodelling potential in preclinical models of pulmonary hypertension by inducing apoptosis and blocking proliferation. This book chapter describes the role of the platelet derived growth factor (PDGF) receptor and its antagonists for treatment of pulmonary hypertension.