Pathogenesis and pathophysiology of pulmonary arterial hypertension

Chang, Sung A

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease with progressive pathology in pulmonary arteries. Although we lack full understanding of PAH pathophysiology, a variety of vascular components are known to be involved in the pathogenesis of PAH. Endothelial dysfunction is one of the most important components, resulting in vasoconstriction and thrombus formation in pulmonary arteries. Muscularization of pulmonary artery with neointima formation contributes to the occlusion of pulmonary arteries. Hyperplasia of smooth muscle cells as well as vasoconstriction are associated with abnormal Ca2+ and K+ transport within smooth muscle cells. Plasma level of 5-HT (serotonin) and expression of its transporters are elevated in PAH, which also mediates vasoconstriction and hyperplasia of smooth muscle cells. On top of the changes found in vessel itself, alterations in extracellular matrix and a cell-to-cell interaction also play an important role in PAH pathogenesis. Inflammatory process with associated cytokines is believed to generate vascular remodeling and as such inhibitor of these processes can be a potential treatment target for PAH. Thanks to all of this pathological interplay briefly described above, plexiform lesion develops at the late stage of PAH and clinically a high pulmonary vascular resistance ensues, consequently resulting in right ventricular failure. Given prognostic relevance of pulmonary vascular resistance, the understanding of pathogenesis and pathophysiology of PAH is essential in guiding a window to developing novel treatment targets and finally improving prognosis as well as increasing a quality of life in PAH patients.