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ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via
Ya Li1, Tian-Tian Wan1, Jia-Xin Li1
1Emergency Medicine Clinical Research Center, Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Molecular Neurobiology
|March 27, 2024
Summary
Myeloid angiotensin-converting enzyme 2 (ACE2) protects against sepsis-associated encephalopathy (SAE) by reducing neuroinflammation and oxidative stress. Upregulating ACE2 may offer a novel therapeutic strategy for SAE.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Sepsis-associated encephalopathy (SAE) involves neuroinflammation and oxidative stress.
- Angiotensin-converting enzyme 2 (ACE2) possesses neuroprotective anti-inflammatory and antioxidant properties.
- The specific role of myeloid ACE2 in SAE pathogenesis requires further investigation.
Purpose of the Study:
- To elucidate the function of myeloid ACE2 in regulating sepsis-associated encephalopathy (SAE).
- To explore the underlying molecular mechanisms by which ACE2 influences SAE.
- To assess the therapeutic potential of modulating ACE2 in SAE.
Main Methods:
- Induction of SAE in ACE2 transgenic, knockout, and bone marrow chimeric mice via cecal ligation and puncture (CLP).
- Analysis of gene and protein expression related to apoptosis, oxidation, and neuroinflammation.
- Measurement of angiotensin peptides and assessment of ACE2 activity, Nrf2, and Sestrin2 expression.
Main Results:
- Cortical ACE2 expression decreased in early sepsis.
- ACE2 overexpression in transgenic mice reduced neuronal apoptosis, oxidative stress, and M1 microglial polarization, increasing Ang-(1-7), Nrf2, and Sestrin2.
- ACE2 deficiency exacerbated SAE, while bone marrow transplantation studies confirmed ACE2's protective role.
Conclusions:
- Myeloid ACE2 plays a crucial protective role in sepsis-associated encephalopathy.
- ACE2 likely exerts its effects by activating the Ang-(1-7)-Nrf2/Sestrin2 signaling pathway.
- Enhancing ACE2 expression and activity presents a potential therapeutic avenue for SAE treatment.
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