Myogenic Anti-Nucleolin Aptamer iSN04 Inhibits Proliferation and Promotes Differentiation of Vascular Smooth Muscle Cells

Biomolecules. 2024 Jun 15;14(6):709. doi: 10.3390/biom14060709.


De-differentiation and subsequent increased proliferation and inflammation of vascular smooth muscle cells (VSMCs) is one of the mechanisms of atherogenesis. Maintaining VSMCs in a contractile differentiated state is therefore a promising therapeutic strategy for atherosclerosis. We have reported the 18-base myogenetic oligodeoxynucleotide, iSN04, which serves as an anti-nucleolin aptamer and promotes skeletal and myocardial differentiation. The present study investigated the effect of iSN04 on VSMCs because nucleolin has been reported to contribute to VSMC de-differentiation under pathophysiological conditions. Nucleolin is localized in the nucleoplasm and nucleoli of both rat and human VSMCs. iSN04 without a carrier was spontaneously incorporated into VSMCs, indicating that iSN04 would serve as an anti-nucleolin aptamer. iSN04 treatment decreased the ratio of 5-ethynyl-2'-deoxyuridine (EdU)-positive proliferating VSMCs and increased the expression of α-smooth muscle actin, a contractile marker of VSMCs. iSN04 also suppressed angiogenesis of mouse aortic rings ex vivo, which is a model of pathological angiogenesis involved in plaque formation, growth, and rupture. These results demonstrate that antagonizing nucleolin with iSN04 preserves VSMC differentiation, providing a nucleic acid drug candidate for the treatment of vascular disease.

Keywords: aptamer; myogenetic oligodeoxynucleotide; nucleolin; vascular smooth muscle cell.

MeSH terms

  • Animals
  • Aptamers, Nucleotide* / pharmacology
  • Cell Differentiation* / drug effects
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular* / cytology
  • Muscle, Smooth, Vascular* / drug effects
  • Muscle, Smooth, Vascular* / metabolism
  • Myocytes, Smooth Muscle* / cytology
  • Myocytes, Smooth Muscle* / drug effects
  • Myocytes, Smooth Muscle* / metabolism
  • Nucleolin*
  • Oligodeoxyribonucleotides / pharmacology
  • Phosphoproteins* / metabolism
  • RNA-Binding Proteins* / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Nucleolin
  • RNA-Binding Proteins
  • Aptamers, Nucleotide
  • Phosphoproteins
  • Oligodeoxyribonucleotides