Exosomal miR-155-5p promote the occurrence of carotid atherosclerosis

J Cell Mol Med. 2024 Nov;28(21):e70187. doi: 10.1111/jcmm.70187.

Abstract

Periodontitis is a significant independent risk factor for atherosclerosis. Yet, the exact mechanism of action is still not fully understood. In this study, we investigated the effect of exosomes-miR-155-5p derived from periodontal endothelial cells on atherosclerosis in vitro and in vivo. Higher expression of miR-155-5p was detected in the plasma exosomes of patients with chronic periodontitis (CP) and carotid atherosclerosis (CAS) compared to patients with CP. Also, the expression level of miR-155-5p was associated with the severity of CP. miR-155-5p-enriched exosomes from HUVECs increased the angiogenesis and permeability of HAECs and promoted the expression of angiogenesis, permeability, and inflammation genes. Along with the overexpression or inhibition of miR-155-5p, the biological effect of HUVECs-derived exosomes on HAECs changed correspondingly. In ApoE-/- mouse models, miR-155-5p-enriched exosomes promoted the occurrence of carotid atherosclerosis by increasing permeable and angiogenic activity. Collectively, these findings highlight a molecular mechanism of periodontitis in CAS, uncovering exosomal miR-155-5p derived periodontitis affecting carotid endothelial cells in an 'exosomecrine' manner. Exosomal miR-155-5p may be used as a biomarker and target for clinical intervention to control this intractable disease in future, and the graphic abstract was shown in Figure S1.

Keywords: LPS; carotid atherosclerosis; chronic periodontitis; exosome; miR‐155‐5p.

MeSH terms

  • Adult
  • Animals
  • Carotid Artery Diseases* / genetics
  • Carotid Artery Diseases* / metabolism
  • Carotid Artery Diseases* / pathology
  • Chronic Periodontitis / genetics
  • Chronic Periodontitis / metabolism
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Female
  • Human Umbilical Vein Endothelial Cells* / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism

Substances

  • MicroRNAs
  • MIRN155 microRNA, human