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Illigens, BM; Casar Berazaluce, A; Poutias, D; Gasser, R; Del Nido, PJ; Friehs, I.
Vascular Endothelial Growth Factor Prevents Endothelial-to-Mesenchymal Transition in Hypertrophy.
Ann Thorac Surg. 2017; 104(3):932-939 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Authors Med Uni Graz:
Gasser Robert
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Number of Figures: 5
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Abstract:
In hypertrophy, progressive loss of function caused by impaired diastolic compliance correlates with advancing cardiac fibrosis. Endothelial cells contribute to this process through endothelial-to-mesenchymal transition (EndMT) resulting from inductive signals such as transforming growth factor (TGF-β). Vascular endothelial growth factor (VEGF) has proven effective in preserving systolic function and delaying the onset of failure. In this study, we hypothesize that VEGF inhibits EndMT and prevents cardiac fibrosis, thereby preserving diastolic function. The descending aorta was banded in newborn rabbits. At 4 and 6 weeks, hypertrophied animals were treated with intrapericardial VEGF protein and compared with controls (n = 7 per group). Weekly transthoracic echocardiography measured peak systolic stress. At 7 weeks, diastolic stiffness was determined through pressure-volume curves, fibrosis by Masson trichrome stain and hydroxyproline assay, EndMT by immunohistochemistry, and activation of TGF-β and SMAD2/3 by quantitative real-time polymerase chain reaction. Peak systolic stress was preserved during the entire observation period, and diastolic compliance was maintained in treated animals (hypertrophied: 20 ± 1 vs treated: 11 ± 3 and controls: 12 ± 2; p < 0.05). Collagen was significantly higher in the hypertrophied group by Masson trichrome (hypertrophied: 3.1 ± 0.9 vs treated: 1.8 ± 0.6) and by hydroxyproline assay (hypertrophied: 2.8 ± 0.6 vs treated: 1.4 ± 0.4; p < 0.05). Fluorescent immunostaining showed active EndMT in the hypertrophied group but significantly less in treated hearts, which was directly associated with a significant increase in TGF-β/SMAD-2 messenger RNA expression. EndMT contributes to cardiac fibrosis in hypertrophied hearts. VEGF treatment inhibits EndMT and prevents the deposition of collagen that leads to myocardial stiffness through TGF-β/SMAD-dependent activation. This presents a therapeutic opportunity to prevent diastolic failure and preserve cardiac function in pressure-loaded hearts. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Animals, Newborn -
Echocardiography -
Epithelial-Mesenchymal Transition - drug effects
Fibrosis - pathology
Fibrosis - prevention & control
Humans -
Hypertrophy, Left Ventricular - diagnosis
Hypertrophy, Left Ventricular - physiopathology
Hypertrophy, Left Ventricular - prevention & control
Myocardium - pathology
Rabbits -
Systole -
Vascular Endothelial Growth Factor A - pharmacology
Ventricular Function, Left - physiology

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