Grant: Project Grant

Cardiovascular disease (CVD) remains the leading cause of death for both men and women in wealthy countries. Even people receiving treatment for modifiable risk factors, like high cholesterol, are still at high risk for heart problems. New treatments are urgently needed, with a key focus on slowing or stopping the buildup of cholesterol and inflammation in the blood vessel walls, the primary cause of CVD. This has led us to explore the lymphatic system, a network of vessels throughout the body, including in the outer layers of blood vessels. The lymphatic system works like a vacuum, removing waste from tissues. A specific type of cells called platelets are crucial for maintaining its function. We have identified factors like apolipoprotein A-1 (APOA1) that help cells interact with platelets. However, while lymph is free of platelets, it contains only small amounts of APOA1. As a result, platelets' protective effects, aided by APOA1, occur mainly on the outside of lymphatic vessels rather than inside them. Extending their influence within the lymphatic system could offer significant benefits. In a previous study, we showed that platelet fragments, known as platelet extracellular vesicles (PEVs), can travel within lymph and deliver platelet contents to tissues that platelets cannot normally reach. Increasing PEVs in lymph improves lymphatic transport and is gaining attention for drug delivery, as platelets uniquely target specific tissues. We hypothesize that encapsulating APOA1 within PEVs may help alleviate lymphatic dysfunction and clear the blood vessel walls. Our goal is to develop a therapy that targets and prevents lymphatic dysfunction, which plays a key role in chronic inflammatory diseases such as CVD. With our expertise and resources, we are uniquely poised to advance this research.