Abstract 16740: MicroRNA Deep Sequencing Reveals Altered Expression in the Left Ventricle in a Rat Model of Chronic Renocardiac Syndrome
Patients with chronic kidney disease (CKD) are at a greatly increased risk of cardiovascular disease, resulting in a state known as chronic renocardiac syndrome (RCS). Several microRNAs (miRNAs) have been shown to be important in pathological cardiac remodeling. The goal of this study was to characterize time-dependent changes in left ventricle (LV) function in a rat model of CKD, 5/6 nephrectomy (5/6 NX), and identify differentially expressed miRNAs that might contribute to the LV changes. We monitored kidney and LV function in Sprague Dawley rats prior to 5/6 NX (n=5) or sham (n=6) surgery and bi-weekly after the surgery throughout the 7 week study. Elevations in plasma creatinine levels and urine output were detected in first week of 5/6 NX (p<0.05 vs. sham). Echocardiography revealed initial compensatory LV remodeling within 3 weeks of 5/6 NX, however signs of LV decompensation were observed by 7 weeks as wall thickness normalized, the chamber dilated (p≤0.01 vs sham) and fractional shortening plummeted (P=0.002 vs. week 3). Histological examination revealed extensive perivascular fibrosis in the LV tissue as further evidence of pathology. We performed miRNA deep sequencing on LV RNA from sham and 5/6 NX animals (2 pools/group; 2-3 animals per pool). Of the 345 known rat miRNAs or homologues detectable in our data set, 34 were differentially expressed following 5/6 NX (p <0.05 vs sham, fold change >2). Of these, 15 were downregulated including miR-9, miR-127, miR-25, and several members of the miR-181 family (miR-181a-2*, -b, and –d). We also found an upregulation of several miRNAs relating to cardiovascular dysfunction, such as miR-21* (miR-21 upregulated by 1.9 fold), miR-132, miR-221 and miR-223. Several differentially expressed miRNAs were not previously known to participate in LV pathogenesis. These data suggest that the development of CKD can modify miRNA expression profiles in the LV, which might subsequently contribute to the development of LV dysfunction in chronic renocardiac syndrome. This is the first study to longitudinally characterize changes in cardiac function in the 5/6 NX model and the first study to examine cardiac miRNA expression in a model of renocardiac syndrome.
- © 2012 by American Heart Association, Inc.