Chapter

Membrane Receptors, Channels and Transporters in Pulmonary Circulation

Volume 661 of the series Advances in Experimental Medicine and Biology pp 435-446

Date:

PDGF Receptor and its Antagonists: Role in Treatment of PAH

  • Friedrich GrimmingerAffiliated withUniversity Hospital, Medical Clinic II/V
  • , Ralph Theo SchermulyAffiliated withDepartment of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research Email author 

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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.

Keywords

Pulmonary hypertension tyrosine kinase PDGF proliferation growth factor