Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/106854
Title: | Establishing a Link between Endothelial Cell Metabolism and Vascular Behaviour in a Type 1 Diabetes Mouse Model | Authors: | Silva, Carolina Sampaio-Pinto, Vasco Andrade, Sara Rodrigues, Ilda Costa, Raquel Guerreiro, Susana Carvalho, Eugenia Pinto-do-Ó, Perpétua Nascimento, Diana S Soares, Raquel |
Keywords: | Carbohydrate and lipid metabolism; Cell sorting; Endothelium metabolism; Genomics; Micro and macrovascular complications | Issue Date: | 2019 | Publisher: | Cell Physiol Biochem Press | Project: | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/NEU/04539/2013/PT POCI-01-0145-FEDER-016385/NETDIAMOND CENTRO-01-0145-FEDER-000012/HealthyAging2020 UID/BIM/04293/2013 EXPL/BIM-MED/0492/2012 SFRH/BPD/88745/2012 SFRH/BD/111799/2015 |
metadata.degois.publication.title: | Cellular Physiology and Biochemistry | metadata.degois.publication.volume: | 52 | metadata.degois.publication.issue: | 3 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/106854 | ISSN: | 10158987 14219778 |
DOI: | 10.33594/000000036 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Establishing-a-link-between-endothelial-cell-metabolism-and-vascular-behaviour-in-a-type-1-diabetes-mouse-modelCellular-Physiology-and-Biochemistry.pdf | 2.88 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
5
checked on Sep 2, 2024
Page view(s)
74
checked on Nov 5, 2024
Download(s)
20
checked on Nov 5, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License