- Title
- MicroRNAs mediate the cardioprotective effect of angiotensin-converting enzyme inhibition in acute kidney injury
- Creator
- Rana, Indrajeetsinh; Velkoska, Elena; Patel, Sheila; Burrell, Louise; Charchar, Fadi
- Date
- 2015
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/99386
- Identifier
- vital:10353
- Identifier
-
https://doi.org/10.1152/ajprenal.00183.2015
- Identifier
- ISSN:0363-6127
- 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 mi- croRNA-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. © 2015 the American Physiological Society. Funding: APP1048285; NHMRC; National Health and Medical Research Council
- Publisher
- American Physiological Society
- Relation
- American Journal of Physiology - Renal Physiology Vol. 309, no. 11 (2015), p. F943-F954
- Rights
- Copyright American Physiological Society
- Rights
- This metadata is freely available under a CCO license
- Subject
- Angiotensin-converting enzyme inhibitors; Car-diorenal cross talk; MicroRNA; MicroRNA-1; MicroRNA-133; MicroRNA-212/132; Subto-tal nephrectomy; Caspase 9; Collagen; Collagen type 1a1; Fibronectin; Forkhead box protein o 3; Forkhead transcription factor; MicroRNA 1; MicroRNA 132; MicroRNA 133; MicroRNA 212; Ramipril; Reduced nicotinamide adenine dinucleotide phosphate oxidase; Transforming growth factor beta; Unclassified drug; Acute kidney failure; Animal experiment; Animal model; Apoptosis; B cell lymphoma cell; Cardiovascular parameters; Controlled study; Drug mechanism; Fibrosis; Gene expression; Gene targeting; Heart muscle cell; Heart protection; Heart ventricle hypertrophy; Nonhuman; Oxidative stress; Rat; 0606 Physiology; 1116 Medical Physiology
- Reviewed
- Hits: 13329
- Visitors: 12455
- Downloads: 1
| Thumbnail | File | Description | Size | Format |
|---|