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BioMed Research International
Volume 2015 (2015), Article ID 765292, 7 pages
http://dx.doi.org/10.1155/2015/765292
Research Article

Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade

1TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany
2Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany
3Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany
4Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, University of Paris-Sud, 92350 Le Plessis-Robinson, France
5Department of Cardiothoracic Surgery and Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA

Received 25 May 2015; Accepted 5 August 2015

Academic Editor: Rei Shibata

Copyright © 2015 Julien Guihaire et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients.