Journal Article

The Roles of Immunity in the Prevention and Evolution of Pulmonary Arterial Hypertension

Nicolls, Mark R., Voelkel, Norbert F.

2017

Overview

Physicians treating patients with pulmonary vascular diseases must account for a wide spectrum of etiologies and presentations that are associated with the syndrome, including HIV/AIDS, connective tissue diseases, chronic obstructive pulmonary disease, and eosinophilic granuloma, all of which have an inflammatory disease component. Patients with lupus erythematosus-associated PAH can respond to steroids (15), patients with HIV/AIDS-associated PAH to antiviral therapy (16), and patients with the rare form of Castleman's lymphoma-associated PAH to rituximab (17). The metabolic theory proposes that the inhibition of glucose oxidation via mitochondrial suppression in pulmonary vascular cells can be observed in established disease and explains a number of features of the PAH vascular phenotype, including endothelial apoptosis resistance and proliferation (25). According to a Mayo Clinic study (26), about 13% of patients with idiopathic PAH display signs and symptoms of the metabolic syndrome, and another study found elevated blood levels of leptin in patients with severe PAH (20). Presence of Inflammatory Cells in the Lungs of Patients with Severe PAH The presence of numerous mast cells, macrophages, lymphocytes, and dendritic cells in and around hypertensive pulmonary vascular lesions is prima facie evidence that these cells may contribute to disease, but definitive evidence is more difficult to obtain and early trials will likely require an empiric approach. Bone morphogenetic protein receptor 2 (BMPR2) haploinsufficiency is associated with increased cytokine release in vascular smooth cells cultured from pulmonary hypertensive animals and patients (33), and the outer adventitial layer is proinflammatory and a key site of immune activation (34,...

• Publisher: Oxford University Press,American Thoracic Society
• Subject: Acquired immune deficiency syndrome / AIDS / Angiogenesis / Animals / Antiviral drugs / Autoimmunity - immunology / Disease / Disease Progression / HIV / Human immunodeficiency virus / Humans / Hypertension, Pulmonary - drug therapy / Hypertension, Pulmonary - immunology / Hypoxia / Immunity - immunology / Immunotherapy / Infections / Inflammation / Inflammation - immunology / Metabolism / Monoclonal antibodies / Mutation / Pathogenesis / Pharmacy / Proteins / Pulmonary / Pulmonary hypertension / Rodents / Shear stress / Targeted cancer therapy / Translational Research, Biomedical / Viral infections