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Angiotensin converting enzyme 2

Angiotensin converting enzyme 2, or ACE2, is an exopeptidase expressed primarily by vascular endothelial cells in the heart and kidneys, but also in respiratory epithelia[1] and in the gastrointestinal tract. It is the target of several coronaviruses, including SARS-CoV and SARS-CoV-2.

2 Biochemistry

ACE2 is a transmembrane metallocarboxypeptidase composed of 805 amino acids. Zinc and chloride ions act as cofactors. The extracellular region consists of two domains, a zinc metallopeptidase domain and a C-terminal collectrin homology domain. The enzyme exhibits homology to angiotensin converting enzyme (ACE).

ACE2 is encoded by the ACE2 gene on the X chromosome (gene locus Xp22.2). In addition to being expressed as a transmembrane protein, a soluble form exists in serum.

3 Function

ACE2 cleaves angiotensin II into angiotensin (1-7), which has anti-inflammatory and lung protective effects via MAS and AT2 receptors.

4 Clinical

4.1 Infectiology

ACE2 serves as a major entry point for some coronaviruses. The pathogens bind to the enzyme with their spike proteins and enter the host cell by subsequent fusion.[2] ACE2 expression increases from the pharynx to the alveoli. In addition, SARS-CoV-2 is thought to have a higher affinity for ACE2 than SARS-CoV. This would explain more rapid and effective viral transmission in the COVID-19 pandemic.

Patients taking drugs that increase the expression of ACE2 - for example, ACE inhibitors or sartans, may be at higher risk of infection and should be switched to calcium antagonists, according to some authors.[3][4] In contrast, the relevant professional societies see no need for action at this time (4/2020).[5][6]

4.2 Pharmacology

Human recombinant ACE2 (APN01) is an experimental therapeutic approach being tested in acute respiratory distress syndrome (ARDS) and pulmonary hypertension.[7] Furthermore, it is currently (2020) being tested for the treatment of COVID-19.[8][9]

5 Sources

1. Hong Peng Jia et al. ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway Epithelia, J Virol. 2005 Dec; 79(23): 14614-14621, retrieved 2020 Mar 27.

2. Kuba K et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury, Nat Med. 2005 Aug;11(8):875-9. epub 2005 Jul 10, retrieved 2020 Mar 30.

3. Zheng Y et al. COVID-19 and the cardiovascular system, Nat Rev Cardiol (2020), retrieved 30 Mar 2020.

4. Fang, L. et al. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?, The Lancet, March 2020, retrieved 27/03/2020.

5. ESC Position Statement of the ESC Council on Hypertension on ACE Inhibitors and Angiotensin Receptor Blockers, retrieved March 27, 2020.

6. The Renal Association, UK position statement for patients: novel corona virus infection and the use of blood pressure medications. retrieved 03/27/2020.

7. Zhang H, Baker A Recombinant human ACE2: acing out angiotensin II in ARDS therapy, Crit Care. 2017 Dec 13;21(1):305, retrieved 2020 Mar 30.

8. Zhang H et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target, Intensive Care Med. 2020 Apr;46(4):586-590, retrieved 2020 Mar 30.

9. clinicaltrials.gov APN01, retrieved 03/30/2020.

 

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  Angiotensin converting enzyme 2   Angiotensin converting enzyme 2, or ACE2, is an exopeptidase expressed primarily by vascular endothelial cells in the heart and kidneys, but also in respiratory epithelia[1] and in the gastrointestinal tract. It is the target of several coronaviruses, including SARS-CoV and SARS-CoV-2. 2 Biochemistry ACE2 is a transmembrane metallocarboxypeptidase composed of 805 amino acids. Zinc and chloride ions act as cofactors. The extracellular region consists of two domains, a zinc metallopeptidase domain and a C-terminal collectrin homology domain. The enzyme exhibits homology to angiotensin converting enzyme (ACE). ACE2 is encoded by the ACE2 gene on the X chromosome (gene locus Xp22.2). In addition to being expressed as a transmembrane protein, a soluble form exists in serum. 3 Function ACE2 cleaves angiotensin II into angiotensin (1-7), which has anti-inflammatory and lung protective effects via MAS and AT2 receptors. 4 Clinical ...
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