New drug targets for pulmonary hypertension: Rho GTPases in pulmonary vascular remodelling.
Rho GTPases, key regulators of actin dynamics, play a major role in vascular processes such as endothelial permeability, cell motility, angiogenesis, nitric oxide production, smooth muscle contractility, cell proliferation and differentiation. In the lung, Rho GTPases control pulmonary vascular tone and remodelling. Their basal activity is important in fetal lung development and vascular adaptation to changes in oxygen levels, but their continuous activation in neonatal or adult lung leads to the development of pulmonary hypertension (PH), a condition characterised by excessive remodelling and hyperconstriction of pulmonary arteries. This review, based on recent molecular, cellular and animal studies, focuses on the current understanding of Rho GTPases signalling in pulmonary vascular physiology and pathophysiology. It also discusses the existing and prospective treatments targeting Rho GTPases in the management of PH.
Wojciak-Stothard
B
B
BHF Laboratories, Department of Medicine, University College London, 5 University Street, WC1E6JJ, UK. b.wojciak-stothard@ucl.ac.uk
D004730:Endothelium, Vascular / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D020741:rho GTP-Binding Proteins