1. Establishing a Link between Endothelial Cell Metabolism and Vascular Behaviour in a Type 1 Diabetes Mouse Model.
- Author
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Silva C, Sampaio-Pinto V, Andrade S, Rodrigues I, Costa R, Guerreiro S, Carvalho E, Pinto-do-Ó P, Nascimento DS, and Soares R
- Subjects
- Animals, Connective Tissue Growth Factor analysis, Connective Tissue Growth Factor metabolism, Diabetes Mellitus, Experimental chemically induced, Diabetes Mellitus, Experimental metabolism, Disease Models, Animal, Endothelial Cells cytology, Fibrosis, Heart Ventricles metabolism, Kidney cytology, Kidney metabolism, Male, Mice, Mice, Inbred C57BL, Microvessels pathology, Myocardium cytology, Myocardium metabolism, Neovascularization, Pathologic, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Receptors, Notch metabolism, Tissue Inhibitor of Metalloproteinase-2 genetics, Tissue Inhibitor of Metalloproteinase-2 metabolism, Transcriptome, Transforming Growth Factor beta genetics, Transforming Growth Factor beta metabolism, Vascular Endothelial Growth Factor Receptor-2 genetics, Vascular Endothelial Growth Factor Receptor-2 metabolism, Diabetes Mellitus, Experimental pathology, Endothelial Cells metabolism, Microvessels physiology
- Abstract
Background/aims: Vascular complications contribute significantly to the extensive morbidity and mortality rates observed in people with diabetes. Despite well known that the diabetic kidney and heart exhibit imbalanced angiogenesis, the mechanisms implicated in this angiogenic paradox remain unknown. In this study, we examined the angiogenic and metabolic gene expression profile (GEP) of endothelial cells (ECs) isolated from a mouse model with type1 diabetes mellitus (T1DM)., Methods: ECs were isolated from kidneys and hearts of healthy and streptozocin (STZ)-treated mice. RNA was then extracted for molecular studies. GEP of 84 angiogenic and 84 AMP-activated Protein Kinase (AMPK)-dependent genes were examined by microarrays. Real time PCR confirmed the changes observed in significantly altered genes. Microvessel density (MVD) was analysed by immunohistochemistry, fibrosis was assessed by the Sirius red histological staining and connective tissue growth factor (CTGF) was quantified by ELISA., Results: The relative percentage of ECs and MVD were increased in the kidneys of T1DM animals whereas the opposite trend was observed in the hearts of diabetic mice. Accordingly, the majority of AMPK-associated genes were upregulated in kidneys and downregulated in hearts of these animals. Angiogenic GEP revealed significant differences in Tgfβ, Notch signaling and Timp2 in both diabetic organs. These findings were in agreement with the angiogenesis histological assays. Fibrosis was augmented in both organs in diabetic as compared to healthy animals., Conclusion: Altogether, our findings indicate, for the first time, that T1DM heart and kidney ECs present opposite metabolic cues, which are accompanied by distinct angiogenic patterns. These findings enable the development of innovative organ-specific therapeutic strategies targeting diabetic-associated vascular disorders., Competing Interests: No conflict of interest., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)
- Published
- 2019
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