Researchers developed a DNA aptamer called iSN04 that targets smooth muscle cells in blood vessels to help prevent plaque buildup, a key issue in atherosclerosis. Atherosclerosis causes arteries to narrow and can lead to heart disease and strokes.
iSN04 interacts with the protein nucleolin in these cells, keeping them stable and potentially offering a new treatment for vascular diseases.
Traditional treatments for atherosclerosis usually lower cholesterol and manage risk factors. A new method targets VSMCs to stabilize plaques and prevent them from breaking apart.
Researchers from Shinshu University, Japan, developed a new nucleic acid drug called iSN04. Led by Associate Professor Tomohide Takaya and first author Ms. Mana Miyoshi, their study was published on June 15, 2024, in Biomolecules.
iSN04 is a DNA aptamer, a short DNA molecule that binds to a specific target. It interacts with nucleolin in VSMCs, a protein involved in plaque instability. By targeting nucleolin, iSN04 helps keep VSMCs stable and reduces plaque formation.
The research team that developed iSN04 had laid the groundwork for this study. Dr. Takaya explained that iSN04 was first found to induce skeletal muscle differentiation in 2021 and later cardiac muscle differentiation in 2023.
This led them to test if it could also promote smooth muscle differentiation. Their study showed iSN04 successfully induces vascular smooth muscle cell (VSMC) differentiation, reducing angiogenesis (new blood vessel growth) in plaques.
iSN04 keeps VSMCs stable and contractile and can enter VSMCs without carriers. It lowers VSMC growth and increases α-smooth muscle actin, a protein marker for contractile VSMCs.
The study also found that iSN04 inhibits angiogenesis in plaques, suggesting it could stabilize plaques and be useful in treating atherosclerosis, cancer, and other conditions. Ms. Miyoshi notes that iSN04’s ability to inhibit angiogenesis and induce VSMC differentiation shows its potential as a therapeutic nucleic acid drug.
Journal reference:
- Mana Miyoshi, Takeshi Shimosato et al., Myogenic Anti-Nucleolin Aptamer iSN04 Inhibits Proliferation and Promotes Vascular Smooth Muscle Cells Differentiation. Biomolecules. DOI: 10.3390/biom14060709.