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J Mol Cell Cardiol. 2013 Oct;63:98-106. doi: 10.1016/j.yjmcc.2013.07.010. Epub 2013 Jul 22.

Impact of the renin-angiotensin system on cardiac energy metabolism in heart failure.

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Department of Pediatrics, University of Alberta, Edmonton, Canada; Department of Pharmacology, University of Alberta, Edmonton, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.


The renin-angiotensin system (RAS) plays a key pathogenic role in heart failure. The adverse effects of angiotensin II (Ang II), a major player of the RAS, contributes to the development of heart failure. Heart failure is accompanied by significant perturbations in cardiac energy metabolism that can both decrease cardiac energy supply and decrease cardiac efficiency. Recent evidence suggests that Ang II might be involved in these perturbations in cardiac energy metabolism. Furthermore, new components of the RAS, such as angiotensin converting enzyme 2 and Ang1-7, have been reported to exert beneficial effects on cardiac energy metabolism. As a result, a further understanding of the relationship between the RAS and cardiac energy metabolism has the potential to improve the control of heart failure, and may lead to the development of new therapies to treat heart failure. This review summarizes what effects the RAS has on cardiac energy metabolism, highlighting how Ang II can induce cardiac insulin resistance and mitochondrial damage, and what role reactive oxygen species and sirtuins have on these processes.


ACC; ACE; ACE2; AMP-activated protein kinase; AMPK; AT1R; AT2R; ATGL; ATP; Acetyl CoA carboxylase; Ang I; Ang II; Ang II type 1 receptor; Ang II type 2 receptor; Angiotensin II; CPT-1; Cardiac energy metabolism; ERRα; G-protein coupled receptor; GLUT; GPCR; HF-PEF; HF-REF; Insulin resistance; MCAD; MCD; MFN2; Mitochondria; NADPH; NOS; PDH; PDK; PKC; PPARα; RAS; ROS; Reactive oxygen species; Sirt; Sirtuin; Sirtuins; TNF-α; VSMC; adenosine triphosphate; adipose triglyceride lipase; angiotensin I; angiotensin II; angiotensin converting enzyme; angiotensin converting enzyme 2; carnitine palmitoyl transferase-1; estrogen related receptor α; glucose transporter; heart failure with preserved ejection fraction; heart failure with reduced ejection fraction; mRNA; malonyl CoA decarboxylase; medium chain acyl CoA dehydrogenase; messenger RNA; mitofusin 2; nicotinamide adenine dinucleotide phosphate; nitric oxide synthase; peroxisome proliferator activated receptor α; protein kinase C; pyruvate dehydrogenase; pyruvate dehydrogenase kinase; reactive oxygen species; renin–angiotensin system; tumour necrosis factor-α; vascular smooth muscle cell

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