Inflammation in Pulmonary Arterial Hypertension

Pulmonary artery hypertension (PAH) is a devastating cardiopulmonary disease characterized by vascular remodeling and obliteration of the precapillary pulmonary arterioles. Alterations in the structure and function of pulmonary vessels result in the resistance of blood flow and can progress to right-sided heart failure, causing significant morbidity and mortality. There are several types of PAH, and the disease can be familial or secondary to an underlying medical condition such as a connective tissue disorder or infection. Regardless of the cause, the exact pathophysiology and cellular interactions responsible for disease development and progression are largely unknown. There is significant evidence to suggest altered immune and vascular cells directly participate in disease progression. Inflammation has long been hypothesized to play a vital role in the development of PAH, as an altered or skewed immune response favoring a proinflammatory environment that can lead to the infiltration of cells such as lymphocytes, macrophages, and neutrophils. Current treatment strategies focus on the dilation of partially occluded vessels; however, such techniques have not resulted in an effective strategy to reverse or prevent vascular remodeling. Therefore, current studies in human and animal models have attempted to understand the underlying pathophysiology of pulmonary hypertension (PH), specifically focusing on the inflammatory cascade predisposing patients to disease so that better therapeutic targets can be developed to potentially reverse or prevent disease progression. The purpose of this chapter is to provide a comprehensive review of the expanding literature on the inflammatory process that participates in PH development while highlighting important and current studies in both animal and human models. While our primary focus will be on cells found in the adaptive and innate immune system, we will review all potential causes of PAH, including cells of the endothelium, pulmonary lymphatics, and genetic mutations predisposing patients. In addition, we will discuss current therapeutic options while highlighting potential future treatments and the questions that still remain unanswered.