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Biomed Res Int. 2015;2015:765292. doi: 10.1155/2015/765292. Epub 2015 Sep 1.

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

Author information

1
TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany.
2
TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany ; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany ; Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany.
3
TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany ; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.
4
Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, University of Paris-Sud, 92350 Le Plessis-Robinson, France.
5
Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany ; Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany.
6
TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany ; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany ; Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany ; Department of Cardiothoracic Surgery and Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.

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.

PMID:
26421302
PMCID:
PMC4569774
DOI:
10.1155/2015/765292
[Indexed for MEDLINE]
Free PMC Article

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