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Cytokines, Chemokines, and Inflammation in Pulmonary Arterial Hypertension

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Lung Inflammation in Health and Disease, Volume I

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1303))

Abstract

According to the World Symposium Pulmonary Hypertension (WSPH) classification, pulmonary hypertension (PH) is classified into five categories based on etiology. Among them, Group 1 pulmonary arterial hypertension (PAH) disorders are rare but progressive and often, fatal despite multiple approved treatments. Elevated pulmonary arterial pressure in patients with WSPH Group 1 PAH is mainly caused by increased pulmonary vascular resistance (PVR), due primarily to sustained pulmonary vasoconstriction and excessive obliterative pulmonary vascular remodeling. Growing evidence indicates that inflammation plays a critical role in the development of pulmonary vascular remodeling associated with PAH. While the role of auto-immunity is unclear, infiltration of inflammatory cells in and around vascular lesions, including T- and B-cells, dendritic cells, macrophages, and mast cells have been observed in PAH patients. Serum and plasma levels of chemokines, cytokines, and autoantibodies are also increased in PAH patients; some of these circulating molecules are correlated with disease severity and survival. Preclinical experiments have reported a key role of the inflammation in PAH pathophysiology in vivo. Importantly, anti-inflammatory and immunosuppressive agents have further exhibited therapeutic effects. The present chapter reviews published experimental and clinical evidence highlighting the canonical role of inflammation in the pathogenesis of PAH and as a major target for the development of anti-inflammatory therapies in patients with PAH.

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Abbreviations

CCL:

chemokine (C-C motif) ligand

CHD:

congenital heart disease

COPD:

chronic obstructive pulmonary disease

CTD:

connective tissue disease

CXCL:

chemokine (C-X-C motif) ligand

CX3CL1:

chemokine (C-X3-C motif) ligand 1

DC:

dendritic cell

EC:

endothelial cell

ECE-1:

endothelin converting enzyme 1

ET-1:

endothelin-1

HIV:

human immunodeficiency virus

LHD:

left heart disease

MCP-1:

monocyte chemotactic protein

MCT:

monocrotaline

PAH:

pulmonary arterial hypertension

PASMC:

pulmonary artery smooth muscle cell

PVR:

pulmonary vascular resistance

RV:

right ventricle

SSc:

systemic sclerosis

TGF-β:

transforming growth factor β

Th:

T-helper

TNF-α:

tumor necrosis factor α

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Authors and Affiliations

  1. College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China

    Shuxin Liang & Haiyang Tang

  2. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

    Shuxin Liang & Haiyang Tang

  3. Department of Medicine, Indiana University, Indianapolis, IN, USA

    Ankit A. Desai

  4. Division of Translational and Regenerative Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA

    Stephen M. Black

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  1. Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY, USA

    Yong-Xiao Wang

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Liang, S., Desai, A.A., Black, S.M., Tang, H. (2021). Cytokines, Chemokines, and Inflammation in Pulmonary Arterial Hypertension. In: Wang, YX. (eds) Lung Inflammation in Health and Disease, Volume I. Advances in Experimental Medicine and Biology, vol 1303. Springer, Cham. https://doi.org/10.1007/978-3-030-63046-1_15

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