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Characterizing Vascular Dysfunction in Genetically Modified Mice through the Hyperoxia Model

Abstract : Modelling is essential for a better understanding of microcirculatory pathophysiology. In this study we tested our hyperoxia-mouse model with healthy and non-healthy mice. Animals (n = 41) were divided in groups-a control group, with 8 C57/BL6 non-transgenic male mice, a diabetic group (DB), with 8 C57BLKsJ-db/db obese diabetic mice and the corresponding internal controls of 8 age-matched C57BLKsJ-db/+ mice, and a cardiac hypertrophy group (CH), with 9 FVB/NJ cα-MHC-NHE-1 transgenic mice prone to develop cardiac failure and 8 age-matched internal controls. After anesthesia, perfusion data was collected by laser Doppler flowmetry (LDF) during rest (Phase 1), hyperoxia (Phase 2), and recovery (Phase 3) and compared. The LDF wavelet transform components analysis (WA) has shown that cardiorespiratory, myogenic, and endothelial components acted as main markers. In DB group, db/+ animals behave as the Control group, but WA already demonstrated significant differences for myogenic and endothelial components. Noteworthy was the increase of the sympathetic components in the db/db set, as in the cardiac overexpressing NHE1 transgenic animals, reported as a main component of these pathophysiological processes. Our model confirms that flow motion has a universal nature. The LDF component's WA provides a deeper look into vascular pathophysiology reinforcing the model's reproducibility, robustness, and discriminative capacities.
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Submitted on : Wednesday, February 5, 2020 - 10:54:23 AM
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Luis Monteiro Rodrigues, Henrique Nazaré Silva, Hugo Ferreira, Alain-Pierre Gadeau. Characterizing Vascular Dysfunction in Genetically Modified Mice through the Hyperoxia Model. International Journal of Molecular Sciences, MDPI, 2019, 20 (9), pp.2178. ⟨10.3390/ijms20092178⟩. ⟨inserm-02467674⟩



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