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PLoS One. 2013 Jul 25;8(7):e69470. doi: 10.1371/journal.pone.0069470. Print 2013.

Heme oxygenase-1 and inflammation in experimental right ventricular failure on prolonged overcirculation-induced pulmonary hypertension.

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Laboratory of Physiology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.


Heme oxygenase (HO)-1 is a stress response enzyme which presents with cardiovascular protective and anti-inflammatory properties. Six-month chronic overcirculation-induced pulmonary arterial hypertension (PAH) in piglets has been previously reported as a model of right ventricular (RV) failure related to the RV activation of apoptotic and inflammatory processes. We hypothesized that altered HO-1 signalling could be involved in both pulmonary vascular and RV changes. Fifteen growing piglets were assigned to a sham operation (n = 8) or to an anastomosis of the left innominate artery to the pulmonary arterial trunk (n = 7). Six months later, hemodynamics was evaluated after closure of the shunt. After euthanasia of the animals, pulmonary and myocardial tissue was sampled for pathobiological evaluation. Prolonged shunting was associated with a tendency to decreased pulmonary gene and protein expressions of HO-1, while pulmonary gene expressions of interleukin (IL)-33, IL-19, intercellular adhesion molecule (ICAM)-1 and -2 were increased. Pulmonary expressions of constitutive HO-2 and pro-inflammatory tumor necrosis factor (TNF)-α remained unchanged. Pulmonary vascular resistance (evaluated by pressure/flow plots) was inversely correlated to pulmonary HO-1 protein and IL-19 gene expressions, and correlated to pulmonary ICAM-1 gene expression. Pulmonary arteriolar medial thickness and PVR were inversely correlated to pulmonary IL-19 expression. RV expression of HO-1 was decreased, while RV gene expressions TNF-α and ICAM-2 were increased. There was a correlation between RV ratio of end-systolic to pulmonary arterial elastances and RV HO-1 expression. These results suggest that downregulation of HO-1 is associated to PAH and RV failure.

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