Lymphatic and Blood Thrombotic Vascular Signaling
Regulation of blood and lymphatic clotting is crucial for development and healing.
The lymphatics arise from the blood vascular system and are important in tissue healing after injury. As a one-way system, the lymphatics utilize valves to prevent backflow of fluid. Both the blood and lymphatic systems utilize anti-thrombotic mechanisms to prevent clotting. Our lab has a longstanding history of studying the mechanism of platelet activation in which lymphatic endothelial Podoplanin activates platelet CLEC2 receptors to drive an inter-vascular form of hemostasis known as lympho-venous hemostasis. More recently, our lab has shown that movement of lymph fluid through lymphatic vessels is important to promote lymphatic valve development (JCI 2015) and prevent clots in blood vessels (JCI 2019). Furthermore, damage to lymphatics prevents healing after injury (JCI 2019, Blood 2019). We are now investigating the role of lymphatics and thrombosis in other organs, such as the gut, heart, and placenta in development and response to injury.
- Igor Brodsky (University of Pennsylvania)
See the below recent publications related to this project:
Genetic blockade of lymphangiogenesis does not impair cardiac function after myocardial infarction
Keller et al. 2021, Journal of Clinical Investigation. https://www.jci.org/articles/view/147070
Hemodynamic regulation of perivalvular endothelial gene expression prevents deep venous thrombosis
Welsh et al. 2019, Journal of Clinical Investigation. https://www.jci.org/articles/view/124791
John and his paper were featured on the podcast "Beyond the Abstract." Listen here.
Hemostasis stimulates lymphangiogenesis through release and activation of VEGFC
Lim et al. 2019, Blood. https://doi.org/10.1182/blood.2019001736
Lymphatic impairment leads to pulmonary tertiary lymphoid organ formation and alveolar damage
Reed et al. 2019, Journal of Clinical Investigation. https://www.jci.org/articles/view/125044
Lymph flow regulates collecting lymphatic vessel maturation in vivo
Sweet et al. 2015, Journal of Clinical Investigation. https://www.jci.org/articles/view/79386