Primary pulmonary hypertension: molecular basis and potential for therapy.
Primary pulmonary hypertension (PPH) is defined clinically by sustained elevation of pulmonary arterial pressure without a demonstrable cause, and is a progressive, often-fatal disease. PPH can be associated with ingestion of appetite suppressants, human immunodeficiency virus infection and certain autoimmune diseases. Familial PPH is known to account for 6% of all cases. Mutations in the gene encoding the bone morphogenetic protein (BMP) type II receptor have been identified in 72% of affected families and 26% of apparently sporadic cases. BMPs are members of the transforming growth factor b superfamily and affect intracellular signalling via Smads and mitogen-activated protein kinases. Evidence supports a 'two-hit' hypothesis in which PPH is triggered by accumulation of genetic and environmental insults in a susceptible individual. Elucidation of the precise molecular and cellular mechanisms underlying PPH will provide a powerful basis for the development of novel therapeutic strategies in the treatment of this devastating condition.
Division of Respiratory Medicine, Department of Medicine, University of Cambridge, Box 157, Level 5, Addenbrooke Hospital, Hills Road, Cambridge, CB2 2QQ, UK. nr206@cam.ac.uk
Nung
N
Rudarakanchana
Nicholas W
NW
Morrell
D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D012701:Serotonin; D020928:Mitogen-Activated Protein Kinases; D052006:Bone Morphogenetic Protein Receptors, Type II