Pulmonary arterial hypertension: new insights and new hope.
Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by abnormal increased vasoconstriction and vascular remodelling. In this review we discuss the pathophysiology, genetic basis and clinical features of this disorder. Current therapy of PAH is based on an understanding of its pathogenesis, and we review current treatment options based on the pathophysiology of the disease. We discuss three promising novel therapies studied in animal models and human tissue. All three therapies appear to prevent and reduce pulmonary arterial medial hyperplasia through their anti-proliferative and/or pro-apoptotic effects: serotonin transporter inhibitors by blocking serotonin uptake; dichloroacetate by activating voltage-gated potassium channels; and simvastatin by preventing activation of small GTPases.
Martin
Kevin B
KB
Pulmonary & Critical Care, Department of Medicine, Brown Medical School, Providence VA Medical Center, Providence, RI, USA.
Klinger
James R
JR
Rounds
Sharon I S
SI
D000818:Animals; D003999:Dichloroacetic Acid / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D015507:Drugs, Investigational; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D015221:Potassium Channels / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D014655:Vascular Resistance / Q000187:drug effects / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D015507:Drugs, Investigational; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015221:Potassium Channels; D012702:Serotonin Antagonists; D014665:Vasodilator Agents; D003999:Dichloroacetic Acid; D019821:Simvastatin