Simultaneous late-gadolinium enhancement and T1 mapping of fibrosis and a novel cell-based combination therapy in hypertensive mice - 13/01/23
Abstract |
Fibrosis is a hallmark of chronic hypertension and disrupts the viability of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) post-transplantation. This study thus, determined whether the anti-fibrotic drug, serelaxin (RLX), could enhance the therapeutic effects of BM-MSCs or BM-MSC-derived exosomes (BM-MSC-EXO) in hypertensive mice. Left ventricular (LV) fibrosis in particular was assessed using conventional histological staining and non-invasive cardiac magnetic resonance imaging (CMRI). CMRI was employed using a novel magnetisation prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence to simultaneously perform late gadolinium enhancement imaging and T1 mapping. Adult male C57BL/6 mice were uninephrectomised, received deoxycorticosterone acetate and saline to drink (1 K/DOCA/salt) for 21 days, whilst control mice were given normal drinking water for the same time-period. On day 14 post-injury, subgroups of 1 K/DOCA/salt-hypertensive mice were treated with RLX alone or in combination with BM-MSCs or BM-MSC-EXO; or the mineralocorticoid receptor antagonist, spironolactone. At day 21 post-injury, LV and kidney histopathology was assessed, whilst LV fibrosis and function were additionally analysed by CMRI and echocardiography. 1 K/DOCA/salt-hypertensive mice developed kidney tubular injury, inflammation, fibrosis, and more moderate LV hypertrophy, fibrosis and diastolic dysfunction. RLX and BM-MSCs combined provided optimal protection against these pathologies and significantly reduced picrosirius red-stained organ fibrosis and MP2RAGE analysis of LV fibrosis. A significant correlation between MP2RAGE analysis and histologically-stained interstitial LV fibrosis was detected. It was concluded that the MP2RAGE sequence enhanced the non-invasive CMRI detection of LV fibrosis. Furthermore, combining RLX and BM-MSCs may represent a promising treatment option for hypertensive cardiorenal syndrome.
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Abbreviations : 1 K, ACEi, BM-MSCs, bpm, CKD, CMRI, CVD, DOCA, DPTA, ECM, ECV, EDV, EF, ENDOarea;d, ENDOarea;s, ESRD, ESV, FS, Gd, GLS, H&E, H2, IHC, IVRT, LGE, LV, LVPWT, MMP, MP2RAGE, rLSR, RLX, RXFP1, SBP, TIs
Keywords : Hypertension, Cardiorenal syndrome, Fibrosis, Cardiac MRI, Relaxin, Bone marrow-MSCs
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Vol 158
Article 114069- février 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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