Endothelial-targeting miR-145 micelles restore barrier function and exhibit atheroprotective effects

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Nanomedicine

Background:

• Atherosclerosis is a leading global cause of death, characterized by endothelial plaque buildup.
• MicroRNA-145-5p (miR-145) is downregulated in atherosclerosis and promotes a healthy vascular smooth muscle cell (VSMC) phenotype.
• Previous studies utilized miR-145 micelles targeting VSMC via CCR2; however, endothelial cell effects remain unexplored.

Purpose of the Study:

• To evaluate the in vitro therapeutic effects of miR-145 micelles on endothelial cells in atherosclerosis.
• To optimize MCP-1 peptide density for enhanced endothelial cell binding.
• To assess miR-145 micelle impact on endothelial cell function and integrity.

Main Methods:

• Optimized MCP-1 peptide density on micelle surfaces for activated endothelial cell binding.
• Loaded miR-145 into micelles at an optimal MCP-1 ratio.
• Treated activated endothelial cells with miR-145 micelles and analyzed gene expression, tight junction integrity, and monocyte migration.

Main Results:

• Efficient miR-145 transfection into activated endothelial cells.
• Upregulation of atheroprotective genes and suppression of atherogenic genes.
• Enhanced endothelial tight junction integrity and reduced monocyte migration.

Conclusions:

• miR-145 micelles effectively modulate endothelial cell function during atherosclerosis.
• This nanotherapy restores endothelial cell health by improving gene expression and barrier function.
• miR-145 micelles represent a promising nanotherapeutic for cardiovascular disease treatment.