Pathogenesis of Pulmonary Hypertension

Pulmonary arterial hypertension (PAH), although rare, is a progressive disease with a high morbidity and mortality rate. In 1981, Ernst von Romberg, a German physician described pulmonary vascular lesions as “pulmonary vascular sclerosis”, the first description of histological changes in PAH [Fishman 2004]. The average survival time for untreated patient is around 2.8 yrs [D’Alonzo 1991]. Despite remarkable progress made since then, the patho‐ genesis of PAH, however, is not yet well understood; because a large number of cardiopul‐ monary and systemic diseases can lead to PAH, and in addition, multiple signaling pathways have been implicated. Current advances in therapy, have improved the quality of life and delayed the progression of the disease, but have not provided a cure. Lack of cure in PAH is further underscored by a recent study showing persistent large plexiform lesions and inflam‐ matory infiltrates in patients despite having been on a long term prostacyclin therapy [Pogoriler 2012]. One of the main reasons for the failure of therapy is that the diagnosis is often made late because of vague symptoms; and by the time the diagnosis is made extensive pathologic changes have already taken place in pulmonary vasculature. From experimental studies, it is clear that pathological changes in the vasculature occur before the onset of PAH [Huang 2010]. Another problem is that a large number of signaling molecules implicated in PAH may not be relevant in all patients; and the activation of some of these molecules may depend on the stage of the disease.