title: Molecular pathogenesis of pulmonary arterial hypertension.
abstract: Recent clinical and experimental studies are redefining the cellular and molecular bases of pulmonary arterial hypertension (PAH). The genetic abnormalities first identified in association with the idiopathic form of PAH--together with a vast increase in our understanding of cell signaling, cell transformation, and cell-cell interactions; gene expression; microRNA processing; and mitochondrial and ion channel function--have helped explain the abnormal response of vascular cells to injury. Experimental and clinical studies now converge on the intersection and interactions between a genetic predisposition involving the BMPR2 signaling pathway and an impaired metabolic and chronic inflammatory state in the vessel wall. These deranged processes culminate in an exuberant proliferative response that occludes the pulmonary arterial (PA) lumen and obliterates the most distal intraacinar vessels. Here, we describe emerging therapies based on preclinical studies that address these converging pathways.
authors.affiliation: Stanford University School of Medicine, Stanford, California 94305-5162, USA. marlener@stanford.edu
authors.forename: Marlene
authors.initials: M
authors.lastname: Rabinovitch
mesh_terms: D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000502:physiology; D004967:Estrogens / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D009154:Mutation; D010196:Pancreatic Elastase / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism
chemical_list: D004967:Estrogens; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II; D010196:Pancreatic Elastase