Introduction

Primary pulmonary hypertension (PPH) is a progressive and fatal disease, whose pathobiology has been elusive. It is clear, however, that the initial explanations that this was a disease of vasoconstriction of the pulmonary vasculature was a gross oversimplification of the biological mechanisms that are involved [1]. With our better understanding of vascular biology and the various mediators involved in the regulation of vascular tone and growth, we now realize that a number of pathways may be involved in what we call PPH, and that many different cell types within the arteries may be implicated in the aetiology. For example, some have suggested that an abnormality in the endothelium can account for the changes that are noted in both the intima and media [2].However, it is also possible that a primary abnormality of the pulmonary artery smooth muscle cell or the extracellular matrix may be causative in this disease. Given the heterogeneous nature of the pathological changes that have been described in patients with primary and secondary forms of pulmonary arterial hypertension, it is likely that more than one abnormality is playing a key role [3,4].Nonetheless, over recent years in treating patients with PPH there has been considerable progress that has arisen from our attempts to understand the pathogenesis of the disease.

The genetic basis of primary pulmonary hypertension

A familial pattern of disease transmission for PPH has been well characterized. Recently, the gene for familial PPH, known as PPH-1, has been described [5]. It is autosomal dominant with markedly reduced penetrance, and is located on chromosome 2q33 (Chapter 2).