Candesartan Reduces Neuronal Apoptosis Caused by Ischemic Stroke via Regulating the FFAR1/ITGA4 Pathway

Area of Science:

• Neuroscience
• Molecular Biology
• Cardiovascular Research

Background:

• Ischemic stroke (IS) involves brain tissue damage due to reduced blood flow.
• The precise molecular mechanisms underlying IS-induced cell damage require further elucidation.
• Cerebral ischemia represents the primary subtype of IS contributing to neuronal injury.

Purpose of the Study:

• To investigate the role of FFAR1 as a hub gene in ischemic stroke.
• To explore the therapeutic potential of candesartan targeting FFAR1 in IS.
• To elucidate the FFAR1/ITGA4 axis in regulating neuronal apoptosis during cerebral ischemia.

Main Methods:

• Utilized oxygen-glucose deprivation/reoxygenation (OGD/R) models in PC12 cells.
• Assessed FFAR1 expression and its impact on cell viability and apoptosis.
• Investigated the effects of FFAR1 deficiency, overexpression, and candesartan treatment.
• Analyzed the expression of ITGA4, Bax, and Cleaved Caspase-3.

Main Results:

• FFAR1 expression was upregulated in OGD/R-treated PC12 cells.
• FFAR1 deficiency decreased cell viability and increased apoptosis, effects reversed by FFAR1 overexpression.
• Candesartan treatment enhanced cell viability and reduced apoptosis.
• FFAR1 deficiency counteracted the protective effects of candesartan by downregulating Bax and Cleaved Caspase-3, while ITGA4 expression was also elevated.

Conclusions:

• FFAR1 acts as a crucial hub gene in the context of ischemic stroke.
• Candesartan demonstrates potential in mitigating neuronal apoptosis via the FFAR1/ITGA4 pathway.
• The FFAR1/ITGA4 axis presents a novel therapeutic target for managing ischemic stroke.