Researchers identify a protein vital to endothelial wound healing after surgery

Surgeons in the United States perform nearly 600,000 coronary artery stent procedures and bypass surgeries every year.

They are the most common cardiovascular operations, and yet many fail within a few years because treatment damages the endothelium - a microscopically thin layer of cells lining blood vessels. Healthy endothelial cells are crucial to healing and long-term success.

Now, Scott Johnstone, an assistant professor with Virginia Tech's Fralin Biomedical Research Institute at VTC, and collaborators have identified a protein vital to the healing process. The study was published this month in Heart and Circulatory Physiology.

"For the first time in a living, functioning system, we understand pathways that are super important for endothelial wound healing to occur," said Johnstone, who is part of the research institute's Center for Vascular and Heart Research. "This is crucial when we're thinking about drug treatments, to ensure we don't interfere with the normal healing process."

The study aimed to discover how endothelial cells recover and vessels heal normally when torn or broken in surgery, to learn how to aid healing.

Endothelial cells line every blood vessel in the body in a layer just a single-cell thick. They are around 10 times thinner than a human hair, but they form one of the most important barriers in our body controlling blood vessel health.

In a previous study, Johnstone found the endothelium is often damaged or lost during heart coronary bypass operations that use a section of saphenous vein transplanted from the leg. It's also well-known that when stents are applied, the endothelium is destroyed and won't regrow over the stent.

Impaired endothelium repair is at the center of why some surgeries fail. When the endothelium is lost, it can lead to an expanded immune response by the body where other cells arrive and block the vessel over again."

Scott Johnstone, assistant professor, Virginia Tech's Fralin Biomedical Research Institute

A protein called connexin 43, which forms channels between cells to allow them to signal to each other and coordinate their responses, is known to be involved in skin wound healing, but the protein's role in endothelial healing was unknown.

Johnstone and his team analyzed nearly 11,000 individual cells from mouse blood vessels to learn whether connexin 43 plays a part in vessel healing. They found that after injury, endothelial cells produced more of the protein. When the researchers deactivated the gene in mice, healing slowed significantly - suggesting connexin 43 helps blood vessels recover after damage.

This suggests that connexin 43 helps the blood vessel heal after damage. Johnstone and his team think the protein could be a target for new therapies to improve recovery and reduce complications after vascular surgery.

"We want to find out how to get back to a healthy vessel, so we need to understand what makes a healthy vessel," said Johnstone, who also holds a faculty appointment in Virginia Tech's Department of Biological Sciences.. "And if we can do that, we can inform doctors what types of treatments may stop these essential cells from healing a vessel to allow it to perform in the way that it should."

This study was funded by the American Heart Association, the National Institutes of Health, Virginia Tech, and the Seale Innovation Fund at the Fralin Biomedical Research Institute.