Abstract 17481: MicroRNAs Mediate the Protective Effect of Angiotensin Converting Enzyme Inhibition (ACEi) on the Heart in Rat Model of Acute Kidney Injury
Introduction: Cardiovascular complications are common in patients with kidney disease. MicroRNAs play an important role in regulating cell death pathways and cardiac hypertrophy but it is not known whether cardiac microRNAs contribute to cardio-renal cross talk. microRNA-1 and microRNA-133 are associated with cardiac fibrosis and apoptosis after myocardial infarction, whilst microRNA-212/132 is associated with cardiac hypertrophy.
Aim: Using a rat model we investigated whether acute kidney injury leads to changes in cardiac microRNAs (1,133,212 and 132) and their gene targets. We also tested the effect of treatment with the angiotensin converting enzyme inhibitor (ACEi) ramipril on these cardiac microRNAs.
Methods: Heart tissues were collected from rats 10 days after subtotal nephrectomy (STNx) surgery, where one kidney was removed and the other partially ligated (n=9), from sham animals (n=9), and from STNx rats treated with ramipril (n=9). RNA was extracted from the left ventricle and quantitative real time PCR was used to measure microRNA and their target gene expression levels.
Results: In rats with renal injury, there was a significant increase in left ventricular hypertrophy (P<0.05 vs sham). There was also a significant increase in expression of cardiac microRNA-212 (2 fold, P<0.05 vs Sham) and microRNA-132 (3 fold, P<0.05 vs Sham). Ramipril treatment in STNx rats attenuated the increase in microRNA-212 and caused a significant increase in expression of microRNA-133 (P<0.001 vs Sham, P<0.001 vs STNx+Veh) and microRNA-1 (P<0.01 vs Sham, P<0.01 vs STNx+Veh). Renal injury induced left ventricular hypertrophy was attenuated in ramipril treated STNx rats (P<0.001 vs STNx+Veh). We also found altered expression of caspase 9, fibronectin 1, collagen 1A1 and forkhead box O3, all known for their involvement in the regulation of apoptosis, fibrosis and hypertrophy in cardiac cells, whilst being targets for the above microRNAs.
Conclusions: The involvement of microRNAs in cardiac pathologies associated with kidney injury is a novel finding of our study. Our finding suggests an involvement of microRNA-1, microRNA-133 and microRNA-212/132 in the cardioprotective action of ACE inhibition in acute kidney injury.
Author Disclosures: I. Rana: None. E. Velkoska: None. L.M. Burrell: None. F.J. Charchar: None.
- © 2014 by American Heart Association, Inc.