Recent insights into the pathogenesis and therapeutics of pulmonary hypertension.
The normal adult pulmonary circulation is a low-pressure, high-capacity circuit. Pulmonary vascular resistance is regulated by alveolar oxygen tension, potassium channels and a variety of locally produced and circulating vasoactive factors. Perturbations of these systems may contribute to the pathogenesis of pulmonary hypertension. Recently, mutations in BMPR2 and ALK-1, genes that encode members of the transforming growth factor-beta (TGF-beta) receptor superfamily, have been found in patients with primary pulmonary hypertension. These observations provide a novel insight into the pathogenesis of primary pulmonary hypertension, and emphasize the importance of the integrity of the TGF-beta receptor family in the maintenance of normal pulmonary vascular structure and function. This review discusses the latest developments in the field of pulmonary vascular biology and the prospects for improving the treatment of pulmonary hypertension.
Strange
Julian W
JW
Section on Clinical Pharmacology, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
Wharton
John
J
Phillips
Peter G
PG
Wilkins
Martin R
MR
D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000628:therapy*; D000860:Hypoxia / Q000150:complications; D008297:Male; D009154:Mutation; D015221:Potassium Channels / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011651:Pulmonary Artery / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000627:therapeutic use
D015221:Potassium Channels; D014665:Vasodilator Agents; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II