title: Discovery of a murine model of clinical PAH: Mission impossible?
abstract: Pulmonary arterial hypertension (PAH) is a lung vascular disease characterized with a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling resulting in right heart failure and premature death. In this brief review, we document the recent advances in identifying genetically modified murine models of PH, with a focus on the recent discovery of the mouse model of Tie2 Cre-mediated deletion of prolyl hydroxylase 2, which exhibits progressive obliterative vascular remodeling, severe PAH, and right heart failure, thus recapitulating many of the features of clinical PAH. We will also discuss the translational potential of recent findings arising from experimental studies of murine PH models.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA. Electronic address: yyzhao@uic.edu.
authors.forename: You-Yang
authors.initials: YY
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D062186:Arterial Pressure / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000172:deficiency* / Q000235:genetics; D019426:Integrases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D042787:Receptor, TIE-2 / Q000235:genetics; D012720:Severity of Illness Index; D066253:Vascular Remodeling / Q000187:drug effects; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000959:Antihypertensive Agents; D051792:Basic Helix-Loop-Helix Proteins; D020536:Enzyme Activators; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D019426:Integrases; D042787:Receptor, TIE-2; D000099162:Endothelial PAS Domain-Containing Protein 1; C490189:Egln1 protein, mouse; C079086:Tek protein, mouse; C045073:Cre recombinase
keywords: Animal model; Endothelium; Hypoxia inducible factor; Prolyl hydroxylases; Vascular remodeling