Other chemical exposures besides drugs such as ACE inhibitors (ACE-Is) and angiotensin II receptor blocker (ARBs) can influence the expression of ACE2.  The following have been shown to increase ACE2 expression levels:

- increased dietary potassium
- intermittent fasting
- nicotine
- Vitamin D
- compounds that interact with SIRT1

Michigan State University

- drug mediators
- non-drug mediators
- genetic mediators
- disease states

Mediators that Infleunce ACE2 Expression

McLachlan, C. S. (2020). The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms. Clinical Hypertension, 26(1), 1-3.
https://clinicalhypertension.biomedcentral.com/articles/10.1186/s40885-020-00147-x

The angiotensin-converting enzyme 2
(ACE2) receptor in the prevention and
treatment of COVID-19 are distinctly
different paradigms

Non-Drug Exposures that Increase ACE2 Expression

Sirtuin 1 (SIRT1) is a gene that is expressed next to the promoter region of the ACE2 gene.  Increased expression or activation of SIRT1 is positively associated with ACE2 expression.  Factors that increase SIRT1 expression or activation include:

- calorie restriction
- resveratrol
- Vitamin C
- aspirin
- metformin
- vitamin B3

This may explain why a large Vitamin C dose can possibly have a rescuing effect for COVID-19 patients with severe acute respiratory distress syndrome.

SIRT1 Modulates ACE2 Expression

- Cardiovascular disease (CVD)
- Use of anti-hypertension medications

Factors that can potentially increase ACE2 expression in the Cardiovascular System 

miRNAs that are homologous to the 3' end of the ACE2 gene were assessed using the data set from the Wang research group to determine if ACE2 expression was modulated by smoking.  miR-1246 is complementary to the  3′ untranslated region (3′UTR) of ACE2 mRNA.  Predicted base pairing was assessed using TargetScanHuman 7.2 (http://www.targetscan.org/vert_72/).  Affymetirx miRNA 2.0 arrays and TaqMan PCR reveal that miR-1246 expression is significantly decreased in smokers compared to nonsmokers (**P < 0.01 and ***P < 0.001).  This miRNA may be involved in the mechanism that regulates ACE2 expression in the SAE. 

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