What causes Primary Pulmonary Hypertension (PPH)?

Primary Pulmonary Hypertension (PPH) has no identifiable underlying cause. Primary Pulmonary Hypertension (PPH) is also referred to as Idiopathic Pulmonary Hypertension.

Primary Pulmonary Hypertension (PPH) is an unusually aggressive and often fatal form of Pulmonary Hypertension that commonly affects young people. Whereas it is known that the arterial obstruction is caused by a building up of the smooth muscle cells that line the arteries, the underlying cause of the disease has long been a mystery.

A genetic cause of the familial form of Primary Pulmonary Hypertension (PPH) has been discovered. It is caused by mutations in a gene called BMPR2. BMPR2 encodes a receptor (a transforming growth factor beta type II receptor) that sits on the surface of cells and binds molecules of the TGF-beta superfamily. Binding triggers conformational changes that are shunted down into the cell's interior where a series of biochemical reactions occur, ultimately affecting the cell's behavior. The mutations block this process. This discovery may provide a means of genetic diagnosis and a potential target for the therapy of people with familial (and possibly also sporadic) Primary Pulmonary Hypertension (PPH).