PH is characterised by an increase in pulmonary arterial pressure and progressive obliteration of the vasculature. This results in right ventricular hypertrophy and/or dilatation, subsequently to right heart insufficiency and death from right heart failure. The focus of recent research has been the decoding of a large number of pathogenetic mechanisms at both a molecular and a genetic level. The basis for current treatment approaches is the imbalance between vasoconstriction and vasodilation, with the imbalance observed between proliferation and apoptosis in the vascular wall in affected patients becoming increasingly important. The concept of reverse remodelling is increasingly being picked up for the future development of treatments.
In histological terms, changes are observed in all three layers of the pulmonary arteria vascular wall: concentric intimal proliferation, hypertrophy of the tunica media and adventitial fibroblast proliferation. “Plexiform lesions” (endothelial cell proliferation resembling glomeruli) and blood clots in situ are also typical findings. This “pan-vasculopathy” chiefly affects small pulmonary vessels, known as the resistance vessels.
At a genetic level, various mutations have been detected in the “bone morphogenetic protein receptor II” (BMPR II) gene in heritable PH. These mutations occur in heritable PAH (in 60% of cases) but also in the sporadic form of PAH (in 25% of cases) . The ligands for this receptor are members of the TGF-beta family and are important for the differentiation, proliferation and apoptosis of many types of cell. Activin-like kinase 1 (ALK 1) mutations which have been described in patients with hereditary haemorrhagic telangiectasia and PAH also appear to play a decisive role in the differentiation and stabilisation of blood vessels.