Treating Inflammation Associated with Pulmonary Hypertension: An Overview of the Literature

Abstract

Pulmonary hypertension (PH) comprises five groups of serious clinical entities characterized by pulmonary artery vasoconstriction and vascular remodeling leading to right heart failure and death. In addition to vascular remodeling, recruitment and exaggerated accumulation of several perivascular inflammatory cells is also observed, including macrophages, monocytes, T and B-lymphocytes, dendritic cells and mast cells distributed in pulmonary perivascular spaces and around remodeling pulmonary vessels. Current pulmonary arterial hypertension (PAH)-targeted therapies aim to improve functional capacity, pulmonary hemodynamic conditions, and delay disease progression. Nevertheless, PAH remains incurable, with a poor prognosis and is often refractory to drug therapy, highlighting the need for further research. In the last three decades, the best pathophysiological understanding of PAH has allowed for progression from a disease of little-known pathogenesis, without specific and effective therapy to expanding the arsenal of drugs on a cellular, genetic and molecular basis. This article provides an overview on current knowledge and progress in recent advances in pharmacological therapy in PAH.

Keywords: inflammation; pulmonary arterial hypertension; treatment.

Figure 1

Hemodynamic integration and cell injury and repair that illustrate the cardiopulmonary condition of severe pulmonary arterial hypertension (PAH). Data from Voelkel et al.

Figure 2

Schematic illustration of inflammation and infection-mediated vascular remodeling: upon stimulation by infection and/or inflammation, lung vascular cells produce and release inflammatory mediators (chemokines and cytokines), thereby recruiting the inflammatory cells. Under the coordination of inflammatory mediators, inflammatory cells can promote the release of cytokines and chemokines, which leads to chronic vasoconstriction, vascular remodeling by vascular cell proliferation, collagen deposition and plexiform lesions. The progressive process causes pulmonary arterial hypertension.