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Title: MicroRNAs mediate the cardioprotective effect of angiotensin-converting enzyme inhibition in acute kidney injury
Austin Authors: Rana, Indrajeetsinh;Velkoska, Elena;Patel, Sheila K ;Burrell, Louise M ;Charchar, Fadi J
Affiliation: Austin Health, Heidelberg, Victoria, Australia
School of Science and Technology, Federation University Australia, Ballarat, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 1-Dec-2015
Date: 2015-09-23
Publication information: American Journal of Physiology - Renal Physiology 2015; 309(11):F943-954
Abstract: Cardiovascular disease, including cardiac hypertrophy, is common in patients with kidney disease and can be partially attenuated using blockers of the renin-angiotensin system (RAS). It is unknown whether cardiac microRNAs contribute to the pathogenesis of cardiac hypertrophy or to the protective effect of RAS blockade in kidney disease. Using a subtotal nephrectomy rat model of kidney injury, we investigated changes in cardiac microRNAs that are known to have direct target genes involved in the regulation of apoptosis, fibrosis, and hypertrophy. The effect of treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril on cardiac microRNAs was also investigated. Kidney injury led to a significant increase in cardiac microRNA-212 and microRNA-132 expression. Ramipril reduced cardiac hypertrophy, attenuated the increase in microRNA-212 and microRNA-132, and significantly increased microRNA-133 and microRNA-1 expression. There was altered expression of caspase-9, B cell lymphoma-2, transforming growth factor-β, fibronectin 1, collagen type 1A1, and forkhead box protein O3, which are all known to be involved in the regulation of apoptosis, fibrosis, and hypertrophy in cardiac cells while being targets for the above microRNAs. ACE inhibitor treatment increased expression of microRNA-133 and microRNA-1. The inhibitory action of ACE inhibitor treatment on increased cardiac NADPH oxidase isoform 1 expression after subtotal nephrectomy surgery suggests that inhibition of oxidative stress is also one of mechanism of ACE inhibitor-mediated cardioprotection. These finding suggests the involvement of microRNAs in the cardioprotective action of ACE inhibition in acute renal injury, which is mediated through an inhibitory action on profibrotic and proapoptotic target genes and stimulatory action on antihypertrophic and antiapoptotic target genes.
DOI: 10.1152/ajprenal.00183.2015
ORCID: 0000-0003-1863-7539
Journal: American Journal of Physiology - Renal Physiology
PubMed URL:
Type: Journal Article
Subjects: Angiotensin-converting enzyme inhibitors
Cardiorenal cross talk
Subtotal nephrectomy
Appears in Collections:Journal articles

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