Macrophage exosomal miR-30c-2-3p in atherosclerotic plaques aggravates microglial neuroinflammation during large-artery atherosclerotic stroke via TGF-β/SMAD2 pathway

J Neuroinflammation. 2024 Nov 8;21(1):292. doi: 10.1186/s12974-024-03281-7.

Abstract

Circulating miR-30c-2-3p has been closely related to vascular diseases, however, its role and underlying mechanisms in ischemic stroke remained unclear. Our study addressed this gap by observing elevated levels of exosomal miR-30c-2-3p in patients with acute ischemic stroke due to large artery atherosclerosis. Further investigation revealed that these exosomal miR-30c-2-3p primarily originated from macrophages within atherosclerotic plaques, exacerbating ischemic stroke by targeting microglia. Exosomes enriched with miR-30c-2-3p increased microglial inflammatory properties in vivo and aggravated neuroinflammation by inhibiting SMAD2. In summary, our findings revealed a novel mechanism whereby macrophage-derived foam cells within atherosclerotic plaques secrete exosomes with high levels of miR-30c-2-3p, thus aggravate brain damage during ischemic stroke, which serves as crucial link between the periphery and brain.

Keywords: Atherosclerosis; Exosomes; Inflammation; MiR-30c-2-3p; Microglia.

MeSH terms

  • Animals
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Exosomes* / metabolism
  • Humans
  • Ischemic Stroke / metabolism
  • Ischemic Stroke / pathology
  • Macrophages* / metabolism
  • Macrophages* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Microglia* / metabolism
  • Microglia* / pathology
  • Neuroinflammatory Diseases* / metabolism
  • Neuroinflammatory Diseases* / pathology
  • Plaque, Atherosclerotic* / metabolism
  • Plaque, Atherosclerotic* / pathology
  • Signal Transduction / physiology
  • Smad2 Protein* / metabolism
  • Stroke / metabolism
  • Stroke / pathology
  • Transforming Growth Factor beta* / metabolism

Substances

  • MicroRNAs
  • Smad2 Protein
  • Transforming Growth Factor beta
  • MIRN30b microRNA, human
  • SMAD2 protein, human