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Diabetic Cardiomyopathy pp 349–357Cite as

The Angiotensin-Converting Enzyme 2/Angiotensin-(1-7)/Mas Receptor Axis: A Potential Target for Treating Diabetic Cardiovascular Disease

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Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 9))

Abstract

Activation of the angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin type-1 receptor (AT1) axis in the heart and vasculature plays an important role in the development of diabetic complications. The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis has been shown to oppose the actions of Ang II. Our results have shown that chronic treatment with Ang-(1-7) led to correction of the altered responses to norepinephrine or endothelin-1 and carbachol in the mesenteric bed, carotid, and renal arteries of diabetic rats and improved recovery of left ventricular function from 40 min of global ischemia. We showed that the beneficial effects of Ang-(1-7) on the diabetic vasculature involve inhibition of the detrimental EGFR/ERK1/2/p38MAP kinase pathway. Ang-(1-7) treatment inhibited cardiac NADPH oxidase (NOX) and cardiac nuclear factor-κB (NF-κB) activity and also suppressed the expression of several pro-inflammatory genes involved in the NF-κB signaling pathway, including complement component 3 (C3), interleukin 1-beta (Il-1β), interleukin 6 (Il-6), NACHT-containing protein (Nalp12), and caspase 1 (Casp1). We conclude that activation of the Ang-(1-7)-mediated signal transduction pathway appears to be an important therapeutic strategy to reduce cardiovascular events in diabetic patients.

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Acknowledgments

This work was supported by a grant from Kuwait University Research Sector (MR05/09).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, 24923, Safat, 13110, Kuwait

    Ibrahim F. Benter, Mariam H. M. Yousif & Saghir Akhtar

  2. Faculty of Allied Health, Kuwait University, Safat, Kuwait

    Jasbir S. Juggi

Authors
  1. Ibrahim F. Benter
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  2. Mariam H. M. Yousif
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  3. Jasbir S. Juggi
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  4. Saghir Akhtar
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Corresponding author

Correspondence to Ibrahim F. Benter .

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Editors and Affiliations

  1. Department of Biophysics, University of Ankara, Ankara, Ankara, Turkey

    Belma Turan

  2. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

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Benter, I.F., Yousif, M.H.M., Juggi, J.S., Akhtar, S. (2014). The Angiotensin-Converting Enzyme 2/Angiotensin-(1-7)/Mas Receptor Axis: A Potential Target for Treating Diabetic Cardiovascular Disease. In: Turan, B., Dhalla, N. (eds) Diabetic Cardiomyopathy. Advances in Biochemistry in Health and Disease, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9317-4_22

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