Research Papers:

NOD2 deficiency exacerbates hypoxia-induced pulmonary hypertension and enhances pulmonary vascular smooth muscle cell proliferation

Min-Young Kwon _, Narae Hwang, Young-Jun Park, Mark A. Perrella and Su Wol Chung

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Oncotarget. 2018; 9:12671-12681. https://doi.org/10.18632/oncotarget.23912

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Min-Young Kwon1, Narae Hwang1, Young-Jun Park2, Mark A. Perrella3 and Su Wol Chung1

1School of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea

2Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, South Korea

3Division of Pulmonary and Critical Care, Department of Medicine, and Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

Correspondence to:

Su Wol Chung, email: [email protected]

Keywords: pulmonary hypertension; pulmonary artery smooth muscle cells; NOD2; hypoxia; HIF-1α

Received: February 12, 2017     Accepted: November 03, 2017     Published: January 03, 2018


Expression of nucleotide-binding oligomerization domain protein 2 (NOD2) is upregulated in pulmonary artery smooth muscle cells (PASMCs) during hypoxia. To investigate the involvement of NOD2 in the pulmonary vascular response to hypoxia, we subjected wild-type and NOD2-deficient mice to chronic normobaric hypoxic conditions. Compared to wild-type mice, NOD2-deficient mice developed severe pulmonary hypertension with exaggerated elevation of right ventricular systolic pressure, profound right ventricular hypertrophy and striking vascular remodeling after exposure to hypoxia. Pulmonary vascular remodeling in NOD2-deficient mice was characterized by increased PASMC proliferation. Furthermore, hypoxia-inducible factor-1α expression and Akt phosphorylation were upregulated in PASMCs from NOD2-deficient mice exposed to hypoxia. Our findings revealed that the absence of NOD2 exacerbated hypoxia-induced PASMC proliferation, pulmonary hypertension and vascular remodeling, but had no effect on PASMC migration or contractility.

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