01 March 2017 by İpek Varturk Ozcan

NADPH oxidase 4 is not involved in hypoxia-induced pulmonary hypertension

Chronic exposure to hypoxia induces a pronounced remodeling process of the pulmonary vasculature, leading to pulmonary hypertension. In this regard, reactive oxygen species (ROS), produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), are discussed as triggers for pulmonary vascular remodeling. Recently, we identified Nox4 to be a source of ROS involved in proliferation of pulmonary arterial smooth muscle cells (PASMC). In addition, we observed elevated Nox4 expression in mice suffering from chronic hypoxia-induced pulmonary hypertension, in isolated human and rat PASMC in hypoxia, and in lungs of patients suffering from idiopathic pulmonary arterial hypertension. Here, we aim to investigate the role of Nox4 in pulmonary hypertension in vivo, using constitutive and inducible Nox4 knockout mice.

Hypoxia-induced pathology was analyzed in isolated perfused lungs, by measuring hemodynamic values and in histological sections vascular muscularization was quantified. The degree of pulmonary hypertension was assessed by right ventricular systolic pressure measurements and analysis of right heart. Neither constitutive nor inducible Nox4 knockout mice exhibit any differences in responses to acute or chronic hypoxia when compared to wild-type mice.

Elevated Nox4 levels in pulmonary hypertension and its role in PASMC proliferation suggest Nox4 to be causal for the development of pulmonary hypertension. Therefore Nox4 appeared to be an interesting target to treat pulmonary hypertension. Our current study proves this assumption wrong. Absence and probably also inhibition is not sufficient to prevent hypoxia-induced pulmonary hypertension pathogenesis in vivo.

About the author

profile picture of İpek Varturk Ozcan

İpek Varturk Ozcan

Phd Candidate

ECCPS-Justus Liebig University


Key Contributors

Veith C1, Kraut S1, Wilhelm J1, Sommer N1, Quanz K1, Seeger W1, Brandes2 RP, Weissmann N1, Schroeder K2 1Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Excellence Cluster Cardio-Pulmonary System (ECCPS), 35392 Giessen, Germany; 2Institute for Cardiovascular Physiology, Goethe University Frankfurt, ECCPS, 60590 Frankfurt, Germany;

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