Potential New Treatments for Atherosclerosis

Investigators have discovered that 2 PARP proteins are involved with arterial diseases.

Investigators in a new study recently discovered a potential new target for the treatment of arterial diseases, including atherosclerosis.

In the study, investigators used proteomics to screen molecules, and discovered that PARP9 and PARP14 are involved in macrophage activation, which is linked to arterial disease.

The process behind the activation of macrophages is not completely understood, but previous research has shown that macrophages are important to the progression of atherosclerosis and thrombotic complications.

Atherosclerosis is characterized by a build-up in the artery walls, which causes decreased blood flow. If these plaques rupture, it may cause an acute occlusion of the artery by a clot.

Current treatment options include medications and surgical procedures to open blocked arteries. Since the condition does not typically exhibit symptoms, patients may not know they have atherosclerosis until a plaque ruptures or if blood flow is significantly restricted.

Investigators in the current study, published by Nature Communications, examined atherosclerosis on a protein-level to determine which are heavily involved in the regulation of macrophages. They discovered that the proteins PARP9 and PARP14 were the most involved.

When they silenced PARP14, researchers discovered that macrophage activation increased. However, silencing PARP9 had the opposite effect, decreasing macrophage activation, according to the study.

The investigators hope that their method could potentially be used to streamline the drug development process. Their method hinges on network analysis to predict which pathways are the most likely to control the studied effect, according to the study. This allows investigators to prioritize the designated pathways.

The process speeds up the traditional method, which involves searching through each pathway without knowledge of the likelihood of it affecting their studied effect, the investigators said. The investigators plan to use these findings to create novel targeted treatments for atherosclerosis and other related diseases.

“Macrophage activation plays a role in not only vascular disorders but also various inflammatory and autoimmune diseases,” said researcher Masanori Aikawa, MD, PhD. “These results could provide important information about the mechanisms of these diseases and help to develop much needed new therapeutics.”