Foam cell-derived exosomes: Messengers between atherosclerosis and microglia

Area of Science:

• Neuroscience
• Cardiovascular Science
• Cell Biology

Background:

• Atherosclerosis (AS) is a significant risk factor for vascular cognitive impairment (VCI).
• The precise mechanisms linking AS to VCI, particularly the peripheral-brain communication, remain incompletely understood.
• Microglial dysfunction is implicated in the pathogenesis of VCI.

Purpose of the Study:

• To elucidate the role of foam cell-derived exosomes in mediating AS-induced VCI.
• To identify the molecular axis responsible for the transmission of pathological signals from peripheral AS lesions to the brain.
• To explore potential therapeutic targets for AS-induced VCI.

Main Methods:

• Investigated the molecular cargo of exosomes derived from AS foam cells.
• Utilized cell culture models of microglia and in vivo VCI models.
• Analyzed the miR-101-3p-Nrf2-Slc2a1 signaling pathway in microglia exposed to exosomal contents.
• Assessed microglial function and cognitive performance in VCI models.

Main Results:

• Foam cell-derived exosomes carry specific microRNAs, including miR-101-3p.
• miR-101-3p delivered via exosomes induces redox imbalance and metabolic defects in microglia.
• This exosome-mediated pathway involves the Nrf2-Slc2a1 axis, leading to microglial dysfunction.
• Microglial dysfunction exacerbates VCI pathology in the context of atherosclerosis.

Conclusions:

• Foam cell-derived exosomes act as crucial mediators in the peripheral-brain axis for AS-induced VCI.
• The miR-101-3p-Nrf2-Slc2a1 axis is a key pathway driving microglial dysfunction and VCI pathogenesis.
• Targeting this exosomal pathway presents a promising therapeutic strategy for AS-related cognitive impairment.