#3078 MILD EXPERIMENTAL CKD IS ASSOCIATED WITH MYOCARDIAL FIBROSIS AND NOTCH/HEDGEHOG SIGNALING DYSREGULATION

Abstract Background and Aims Chronic kidney disease (CKD) is an independent cardiovascular risk factor. The initial mechanisms of myocardial remodeling (MR) in CKD are poorly understood. major developmental signaling pathways Notch, Hedgehog, Wnt, Bmp seem to be involved many crucial steps MR (cardiomyocytes survival regeneration, fibrotic response, angiogenesis), while their role due was not previously studied. Phosphate (Pi) essential for cellular its redistribution the compartment could a one MR. Here we investigated involvement Pi/PPi transport, reactivation alterations associated with mild CKD. Method We induce by 3/4 nephrectomy adult male SHRs (SHR-Nx, n=8) normal phosphate intake (0.6%) 2-month follow-up. Controls were sham-operated SHR (SHR-Sham, Wistar Kyoto rats (WKY-Sham, n=8). analyzed chronic injury Pi exchange parameters, serum intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), phosphorus content (ICP-AES), histomorphometry, PiT1 PiT2 expression (IHC), mRNA Slc20a1, Slc20a2, Ankh, Mapk1, Mapk3, Bmp2, Bmp4, Ctnnb1, Fzd2, Sfrp2, Dkk1, Wif1, Numb, Notch1, Jag1, Hes1, Lgr4, Tnfrsf11b, Tnfsf11, Ptch1. Results Systolic blood pressure mass index (MMI) higher vs WKY-Sham (Table 1). Decrease creatinine clearance 30% increase albuminuria corresponded SHR-Nx model In SHR-Nx, interstitial fibrosis significantly (Figure 1), MMI cardiomyocyte diameter did differ compared SHR-Sham Myocardial accompanied myocardium down-regulation PPi-exporter up-regulation Hes1 decline Ptch1 2). found no changes Slc20a1 Slc20a2 levels An appearance PiT2-positive fibroblasts-like cells interstitium apparent (data shown). Conclusion manifested content, fibrosis, dysregulation genes likely related induction myofibroblasts extracellular matrix remodeling.