A rat model of enhanced glycation mimics cardiac phenotypic components of human type 2 diabetes : A translational study using MRI
| Autor: | Bruno Ribeiro, Tiago Rodrigues, Mafalda Sanches, Sónia Gonçalves, Maria João Ferreira, José Sereno, Raquel Seiça, Miguel Castelo-Branco, Bruno Graça, João Castelhano, Christian Neves, Bárbara Oliveiros, Paulo Matafome, Joana Saraiva |
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| Rok vydání: | 2019 |
| Předmět: |
Cardiac function curve
Glycation End Products Advanced Male medicine.medical_specialty Diabetic Cardiomyopathies Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Type 2 diabetes 030204 cardiovascular system & hematology 03 medical and health sciences Ventricular Dysfunction Left 0302 clinical medicine Endocrinology Glycation Risk Factors Diabetes mellitus Internal medicine Internal Medicine Medicine Animals Humans Rats Wistar End-systolic volume Metabolic Syndrome Ejection fraction business.industry Stroke volume Middle Aged medicine.disease Phenotype Magnetic Resonance Imaging Healthy Volunteers Rats Disease Models Animal Diabetes Mellitus Type 2 Female business |
| Zdroj: | Journal of diabetes and its complications. 34(5) |
| ISSN: | 1873-460X |
| Popis: | Background The success of translational research depends on how well animal models mimic the pathophysiology of the human phenotype, and on the identification of disease mechanisms such as enhanced glycation. Methods Here, we studied cardiac MRI and metabolic phenotypes in human type 2 diabetes (N = 106; 55 patients+51 controls) and animal models with distinct levels of fat diet and end glycation products, to model the role of these factors in the cardiac phenotype. We included four groups of rats, designed to evaluate the role of lipid load and glucotoxicity in cardiac function and to correlate these with the cardiac phenotype observed in humans. We also aimed to assess into which extent phenotypes were related to specific risk factors. Results Stroke Volume (SV) and Peak Filling Rate (PFR) measures were similarly discriminative both in humans and animal models, particularly when enhanced glycation was present. Factorial analysis showed that reduction of multidimensionality into common main explanatory factors, in humans and animals, revealed components that equally explained the variance of cardiac phenotypes (87.62% and 83.75%, respectively). One of the components included, both in humans and animals, SV, PFR and peak ejection rate (PER). The other components included in both humans and animals are the following: ESV (end systolic volume), left ventricular mass (LVM) and ejection fraction (EF). These components were useful for between group discrimination. Conclusions We conclude that animal models of enhanced glycation and human type 2 diabetes share a striking similarity of cardiac phenotypic components and relation with metabolic changes, independently of fact content in the diet, which reinforces the role of glucose dysmetabolism in left ventricular dysfunction and provides a potentially useful approach for translational research in diabetes, in particular when testing new therapies early on during the natural history of this condition. |
| Databáze: | OpenAIRE |
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