Abstract 9386: Marfan Syndrome Mouse Model MgΔ Lpn Presents Alterations in Glomerular Architecture and Increased Renal Vascular Resistance. Losartan Treatment Attenuates These Phenotypes

Introduction: Previously, we have shown that mgΔ lpn murine Marfan syndrome (MFS) model with a fibrillin-1 disruption presents increased Metalloproteinase-9 (MMP-9) expression in the cilliary body in eye. MMP-9 has been related to microfibrils degradation. In this study, we examined the fibrillin-1 and MMP-9 distribution in the kidney and their influence on hemodynamics. Hypothesis: The alteration of fibrillin-1 impacts the glomerular architecture and modify renal hemodynamics. Methods: Female mice at 4 months of age were used: MFS mgΔ lpn mice (n=5); mgΔ lpn treated with losartan for 3 months (n=5); and control wild type mice (n=5). The glomerular structure of the kidney was examined by histology. The distribution and quantification of fibrillin-1 and MMP-9 were analyzed by immunofluorescence assay. Blood flow in the aorta and renal artery was monitored with the probe 2SB-T206 of the Transonic Systems, and the cortical micro-hemodynamic of the kidney was examined by SDF video-microscopy (Sidestream Dark Field Imaging). Results: The mgΔ lpn mice showed reduction of fibrillin-1 deposition and an increase in MMP-9 in the entire kidney tissue, including the glomerular structures. In histologic aspects, the glomerulus showed a reduction of the glomerular area, urinary space, and vascular pole area. The reduced glomerulus dimension possibly squeezes the arteriolar system with a subsequent increase of their vascular resistance. In addition, the cortical microvessels showed a significant reduction in blood flow, and there was an increase in the distribution of microvessels with diameters 6 to 8 μm. Blood flow analysis in the mgΔ lpn showed decreased artery renal flow but did not reveal a difference in aorta blood flow when compared to WT animals. These results indicate vascular resistance in the renal artery. Losartan therapy increased fibrillin-1 and decreased MMP-9 quantifications, improved the glomerulus structures and significantly increased the velocity of the microcirculation blood flow. Conclusions: Alterations in fibrillin-1 modify the glomerular structures and impair kidney hemodynamics. Losartan therapy minimized the renal phenotypes.