The defining characteristics of pulmonary arterial hypertension

Pulmonary Arterial Hypertension (PAH) is a multifactorial progressive cardiopulmonary disease characterized by smooth muscle cell proliferation, hypertrophy of the vascular medial layer, arteriolar muscularization and endothelial cell proliferation. The persisting challenge in understanding the pathobiology of PAH is to define how the structural, cellular and molecular characteristics of the normal pulmonary circulation are disrupted in the disease setting. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation and metabolic reprograming in the development of PAH. In this review, we highlight the known characteristic pathological features of human and experimental PAH. Additionally, we discuss how inflammatory signaling, including various chemokines, cytokines, immune cells, macrophages and TGF-β contribute to the PAH phenotype. Finally, we review emerging evidence that disordered cellular energetics and hypoxia signaling is characteristic in PAH. This chapter highlights the complexity and multiple pathobiologic disturbances that are defining characteristics of PAH.