Abstract P213: Western Diet May Modulate Kidney Injury and Albuminuria Differentially in Female Mice Deficient in Mr in the Endothelium versus the Smooth Muscle
Activation of the mineralocorticoid receptor (MR) has been implicated in kidney injury and precipitation of proteinuria. In this regard, diet induced obesity (DIO), a condition of MR activation is characterized by increase in kidney injury and proteinuria. DIO and other conditions of MR activation also manifest vascular dysfunction that may play a role in kidney injury and proteinuria. Vascular dysfunction may be endothelial or smooth muscle mediated. Moreover, MR signaling in the endothelium versus smooth muscle may be important in vascular function. Data from the Jaffe lab and our preliminary data show that deficiency of smooth muscle and endothelial MR plays a protective role from vascular dysfunction such as increased pulse wave velocity and stiffness. However, the role of endothelial specific versus smooth muscle specific MR in kidney injury and proteinuria is not known. Hence, we hypothesized that deficiency of endothelial and smooth muscle specific MRs (ECMRKO and SMMRKO) will protect the mice from Western diet-fed (high fat/high sucrose, WD) kidney injury and proteinuria. We fed female ECMRKO/SMMRKO and their littermate controls WD for 16wks and collected urine and performed imaging, molecular and morphological analyses. We observed significantly less proteinuria in the ECMRKO mice fed WD when compared to their littermates (2.4mg/mg vs. 3.5mg/mg creatinine) (p<0.05), however there was no change in the SMMRKO mice fed a WD when compared to their littermates. Furthermore, we observed significantly less impairment in aortic/renal pulse wave velocity and stiffness in both the ECMRKO/SMMRKO models. Western blots showed that there was a tendency to suppression of MR protein in the ECMRKO on WD. This suppression of MR expression was contemporaneously observed with decreased phosphorylation of ribosomal protein S6 along with reduction in membrane localization suggesting endothelial MR may regulate S6 activation. In summary, our study suggests endothelial specific MR may mediate kidney injury in conditions of MR activation and a lesser role for smooth muscle specific MR.
Author Disclosures: R. Nistala: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Significant; Dialysis Clinic Inc. R. Simpson: A. Employment; Significant; DCI. J. Habibi: None. A. Aroor: None. M. Garro: None. V. DeMarco: None. M. Hayden: None. J. Sowers: None. A. Whaley-Connell: None.
- © 2015 by American Heart Association, Inc.