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Adaptive Immune Cells Contribute to Chronic Hypoxia‐Induced Pulmonary Hypertension
Author(s) -
Maston Levi David,
Resta Thomas C,
Can Judy L,
Giermakowska Wieslawa,
Bosc Laura V González
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1140.10
Subject(s) - pulmonary hypertension , ventricle , medicine , hypoxia (environmental) , immune system , ventricular pressure , right ventricular hypertrophy , muscle hypertrophy , cardiology , inflammation , pulmonary artery , lung , pathophysiology , endocrinology , pathology , blood pressure , immunology , chemistry , organic chemistry , oxygen
Inflammation is a prominent pathologic feature in pulmonary arterial hypertension (PAH) as demonstrated by infiltration of inflammatory cells, including T and B lymphocytes, in the pulmonary vasculature of both patients and animal models. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia (CH) exposure. Therefore, we hypothesized that a lack of inflammatory cells, specifically T and B cells, protects mice from CH‐induced pulmonary hypertension. To test this hypothesis, we assessed indices of pulmonary hypertension in normoxic and CH (P B =380 mmHg, 3 wk) C57BL/6 wild‐type (WT) and RAG1 knockout (KO) mice, which lack mature T and B cells. Consistent with our hypothesis, CH RAG1 KO had a significantly lower peak right ventricular systolic pressure (RVSP) compared to CH WT mice (27.2 vs 37.7 mmHg, n=5 p<0.05). In contrast, RVSP was not different between normoxic RAG1 KO and WT animals (20.95 vs 21.8 mmHg). Additionally, CH RAG1KO mice displayed significantly reduced right ventricular hypertrophy (right ventricle/left ventricle+septum weight of 32.7 vs 40.15 % for CH WT, p<0.05) and pulmonary arterial remodeling (arterial wall thickness of 22.4 vs 28.1 % for CH WT, p<0.05) compared to CH WT mice. Our data suggest that adaptive immune cells contribute to the development of CH‐induced pulmonary hypertension.