MicroRNA-92a Inhibition as an Approach to Reduce Vascular Inflammation
Atherosclerosis, the formation of fatty plaques that weaken and narrow blood vessels, is in part driven by inflammation. Inflammatory signaling in atherosclerotic plaque attracts circulating monocytes that enter tissue from the bloodstream, become dysfunctional macrophages, and die. It also biases those macrophages away from useful behavior related to repairing the plaque, even as the toxicity of the plaque environment destroys them. Blunt approaches to suppressing inflammation have been shown to modestly reverse plaques, but nowhere near as much as is needed to produce a cure. These blunt approaches also have significant long-term negative side-effects as a result of degrading immune function where it is needed and useful. There is always the possibility that more selective ways can be found to reduce only the problematic inflammatory signaling, however, such as the example here. It remains to be seen as to whether this will be more effective in reversing plaque burden.
In vascular diseases like atherosclerosis, arterial walls thicken and harden, disturbing blood flow. That leads to a buildup of plaque, which could ultimately lead to blocked arteries. Studies have linked microRNA-92a (miR-92a) to dysfunction of the endothelial cells that line the inside of blood vessels, which means miR-92a is considered a biomarker of the disease.
While a miR-92a inhibitor treatment exists (and has been tested in animals and humans), it cannot yet be delivered directly to the blood vessel site, and therefore is not as effective as it could be. Several years ago, researchers developed a nanoparticle - a polyelectrolyte complex micelle - to deliver the inhibitor directly to inflamed blood vessel cells. This nanoparticle uses a peptide to target the vascular cell adhesion molecule 1 (VCAM-1), which is found in high levels in inflamed endothelial cells but remains low in healthy cells. Once the peptide finds the molecule, it delivers the miR-92a inhibitor directly to the damaged cells.
The team has tested the nanomedicine in a mouse model and found that it reduces the size of vascular lesions. They also found that the treatment inhibited stenosis, the remodeling of vascular tissue that causes it to close off.