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.
Rudarakanchana
Nung
N
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
Morrell
Nicholas W
NW
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