Lymphatic dysfunction is connected to a variety of diseases, including both cardiovascular disease and cancer. For example, breast cancer cells break away from the primary tumor and travel through the lymphatic system. If left alone, they can spread throughout the body. Lymphatic vessels—which operate in similar ways to the cardiovascular system—are sometimes traumatized by cancer treatment or the removal of lymph nodes, which can lead to lymphedema, or the chronic swelling of a leg or arm.

Working with a sheep model, collaborators from Georgia Tech and the Regenerative Bioscience Center at UGA’s College of Agricultural and Environmental Sciences, removed one of two lymphatic vessels that run parallel to each other in the leg. These are as crucial to lymph flow as the heart is to blood flow, according to the researchers. Under these conditions, they were able to show the beginning of a lymphatic pump cycle and the start of the remodeling and repair stages.

As a result of the remodeling, the team concluded that molecular changes in lymphatic muscle cells enhanced oxidative stress, which typically occurs when the immune system is creating inflammation to fight off bacteria. After a period of six weeks, the team discovered that the remaining lymphatic vessel was working twice as hard to compensate for the oxidative stress.

“One would expect that when you remove the main lymph vessel, in the part that’s lower than the obstruction, it would swell. To our surprise, it only did so minimally,” Peroni said. “It turns out there’s a considerable amount of collateral lymphatic circulation that we were not expecting. At a microscopic level, there’s enough mechanisms by which the body can still recirculate and drain fluids out of the leg, even though the main ‘highway’ is removed.”

The findings follow the same researchers’ previous work which showed similar results in using the rodent tail, one of the oldest and most widely utilized model systems for lymphatic research.

“Perhaps the most important single feature of using a larger model like sheep, versus the historical benchmark of a rodent’s tail, is the gravitational benefits,” Peroni said. “Gravity makes it harder for lymph to be transported from the legs and the lower half of the body, and sheep provide a better gravitational model compared to the consistently flat position of a rodent’s tail. It’s almost identical to wound-healing issues in humans.”

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Journal of Phlebology and Lymphology
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