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  • Correspondence
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Mechanisms by which angiotensin-receptor blockers increase ACE2 levels

Nature Reviews Cardiology volume 17, page 378 (2020)Cite this article

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We read with interest the well-balanced Comment by Zheng and colleagues (COVID-19 and the cardiovascular system. Nat. Rev. Cardiol. 17, 259–260; 2020)1 and their Reply (Reply to: ‘Interaction between RAAS inhibitors and ACE2 in the context of COVID-19’. Nat. Rev. Cardiol. 17, 313–314; 2020)2 to the Correspondence written by Mourad and Levy (Interaction between RAAS inhibitors and ACE2 in the context of COVID-19. Nat. Rev. Cardiol. 17, 313; 2020)3.

We have reported the capacity of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) to increase the left ventricular levels of Ace2 mRNA when given to normotensive rats either under normal conditions4 or following coronary artery ligation5. This work revealed the existence of a negative feedback mechanism in which the angiotensin-converting enzyme 2 (ACE2)–angiotensin-(1–7)–Mas receptor axis counterbalances the pathological effects of angiotensin II6. In their Reply2, Zheng and colleagues suggest that the mechanism underlying the increase in levels of cardiac Ace2 mRNA and ACE2 activity by these drugs was undetermined; we wish to clarify that we did elucidate the mechanism by which these medications augment the expression of ACE2 (refs7,8,9).

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References

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Acknowledgements

The work by the authors described in this Correspondence was carried out with support from the National Heart, Lung, and Blood Institute of the NIH (grant HL-051952).

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Authors and Affiliations

  1. Department of Surgery, Wake Forest School of Medicine, Winston Salem, NC, USA

    Carlos M. Ferrario & Sarfaraz Ahmad

  2. Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, NC, USA

    Carlos M. Ferrario

  3. Department of Anesthesiology, Wake Forest School of Medicine, Winston Salem, NC, USA

    Leanne Groban

Authors
  1. Carlos M. Ferrario
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  2. Sarfaraz Ahmad
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Correspondence to Carlos M. Ferrario.

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Ferrario, C.M., Ahmad, S. & Groban, L. Mechanisms by which angiotensin-receptor blockers increase ACE2 levels. Nat Rev Cardiol 17, 378 (2020). https://doi.org/10.1038/s41569-020-0387-7

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