Dysregulation of micro-RNA 143-3p as a Biomarker of Carotid Atherosclerosis and the Associated Immune Reactions During Disease Progression

J Cardiovasc Transl Res. 2024 Aug;17(4):768-778. doi: 10.1007/s12265-024-10482-1. Epub 2024 Jan 25.

Abstract

Atherosclerosis commonly remains undiagnosed until disease manifestations occur. The disease is associated with dysregulated micro(mi)RNAs, but how this is linked to atherosclerosis-related immune reactions is largely unknown. A mouse model of carotid atherosclerosis, human APOB100-transgenic Ldlr-/- (HuBL), was used to study the spatiotemporal dysregulation of a set of miRNAs. Middle-aged HuBL mice with established atherosclerosis had decreased levels of miR-143-3p in their carotid arteries. In young HuBL mice, early atherosclerosis was observed in the carotid bifurcation, which had lower levels of miR-15a-5p, miR-143-3p, and miR-199a-3p, and higher levels of miR-155-5p. The dysregulation of these miRNAs was reflected by specific immune responses during atheroprogression. Finally, levels of miR-143-3p were 70.6% lower in extracellular vesicles isolated from the plasma of patients with carotid stenosis compared to healthy controls. Since miR-143-3p levels progressively decrease when transitioning between early and late experimental carotid atherosclerosis, we propose it as a biomarker for atherosclerosis.

Keywords: Atherosclerosis; Carotid stenosis; Dyslipidemia; Micro-RNA; T-lymphocytes.

MeSH terms

  • Animals
  • Apolipoprotein B-100* / blood
  • Apolipoprotein B-100* / genetics
  • Biomarkers / blood
  • Carotid Arteries / immunology
  • Carotid Arteries / pathology
  • Carotid Artery Diseases* / blood
  • Carotid Artery Diseases* / genetics
  • Carotid Artery Diseases* / immunology
  • Carotid Stenosis / blood
  • Carotid Stenosis / genetics
  • Carotid Stenosis / immunology
  • Case-Control Studies
  • Disease Models, Animal*
  • Disease Progression*
  • Extracellular Vesicles / genetics
  • Extracellular Vesicles / immunology
  • Extracellular Vesicles / metabolism
  • Female
  • Gene Expression Regulation
  • Genetic Markers
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs* / blood
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Plaque, Atherosclerotic
  • Receptors, LDL / genetics

Substances

  • MicroRNAs
  • Apolipoprotein B-100
  • Receptors, LDL
  • MIRN143 microRNA, human
  • Biomarkers
  • APOB protein, human
  • Genetic Markers