Title:Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
Volume: 23
Issue: 4
关键词:
COVID-19、SARS-CoV-2、血管紧张素转换酶 2、神经炎症、高血压、ACEIs
摘要: Background: Angiotensin-converting enzyme 2 (ACE2) has been reported as a portal
for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently,
scientific strategies to combat coronavirus disease of 2019 (COVID-19) were targeted to arrest
SARS-CoV-2 invasion by blocking ACE2. While blocking ACE2 appears a beneficial approach to
treat COVID-19, clinical concerns have been raised primarily due to the various intrinsic roles of
ACE2 in neurological functions. Selective reports indicate that angiotensin receptor blockers (ARBs)
and angiotensin-converting enzyme inhibitors (ACEIs) upregulate ACE2 levels. ACE2 metabolizes
angiotensin II and several peptides, including apelin-13, neurotensin, kinetensin, dynorphin,
(des-Arg9) bradykinin, and (Lys-des-Arg9)-bradykinin, which may elicit neuroprotective effects.
Since ARBs and ACEIs upregulate ACE2, it may be hypothesized that patients with hypertension
receiving ARBs and ACEIs may have higher expression of ACE2 and thus be at a greater risk of severe
disease from the SARS-CoV-2 infections. However, recent clinical reports indicate the beneficial
role of ARBs/ACEIs in reducing COVID-19 severity. Together, this warrants a further study
of the effects of ACE2 blockades in hypertensive patients medicated with ARBs/ACEIs, and their
consequential impact on neuronal health. However, the associations between their blockade and
any neuroinflammation also warrant further research.
Objective: This review collates mechanistic insights into the dichotomous roles of ACE2 in SARSCoV-
2 invasion and neurometabolic functions and the possible impact of ACE2 blockade on neuroinflammation.
Conclusion: It has been concluded that ACE2 blockade imposes neuroinflammation.