Abstract Body: Introduction: Preeclampsia (PE) patients exhibit left ventricular (LV) hypertrophy and dysfunction during pregnancy. While these clinical findings have been recapitulated in a PE animal model (reduced uterine perfusion pressure; RUPP), mechanisms underlying such adverse cardiac outcomes have not yet been explored. A few recent studies involving models of heart failure have shown that pathogenic effects of microRNAs (miRNAs) are attributed to their regulatory actions on cardiac mitochondria. Hypothesis: Inspired by this literature, we set out to test the hypothesis that cardiac dysfunction in PE is mediated by abnormal miRNA expression, and the resulting mitochondrial dysfunction within the myocardium. Methods: PE was induced in pregnant Sprague Dawley (SD) on gestational day(GD)14. After blood pressure measurements (carotid catheterization) on GD19, whole hearts were excised, weighed, and ventricular tissue was used for miRNA (Qiagen’s miRNeasy Micro Kit) and mitochondria (differential centrifugation) isolations. Small RNA sequencing(s-RNA seq) and mitochondrial experiments were performed by Illumina sequencer (NEXTFLEX Kit) and Oxygraph-2K, respectively. Differentially expression (diff-exp) analysis was conducted using DESeq2 in R (fold change=2, adj p=0.05). Results: PE phenotype in RUPP rats was confirmed by elevated MAP (116.1±1.83 vs.101.3±2.93 mmHg, p=0.0008,n=8) on GD19. Normalized heart weight was higher in RUPPs (0.0033 ±9.98e-005 vs. 0.0029±0.00014, p=0.05, n=7-8) suggesting a hypertrophied heart. S-RNA seq revealed a total of 53 (21 up and 32 down) diff-exp miRNAs in RUPP vs. control rats. The top 5 up (miR-741-5p, miR-1-5p, miR-1b, miR-30b-5p, let-7d-3p) and down (miR-871-5p, miR-2985, miR-185-3p, miR-494-3p, miR-1839-3p) regulated miRNAs included transcripts (miR-1 and miR-494-3p) shown to be implicated in cardiac remodeling. Further, complex III activity was reduced (1785±186.1 vs.2468±223.8nmol e^-/min/mg, p=0.03, n=8) in RUPPs with accompanying increased trend in ROS levels (1.34±0.22 vs. 0.84±0.13nmol e^-/min/mg, n=8, p=0.07) although activities of other complexes or oxygen consumption rates were unchanged. Conclusions: To the best of our knowledge, this is the first study to demonstrate abnormal expression of cardiac miRNAs in association with reduced cardiac mitochondrial function in the RUPP rat model of PE. Our ongoing work will determine whether these dysregulated miRNAs contribute to cardiac dysfunction via mitochondrial perturbations.