Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1016/j.athoracsur.2017.01.112
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- Co-Autor*innen der Med Uni Graz
- Gasser Robert
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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