Functional and Molecular Adaptation of Lymphatic Vessels

Abstract

We developed a bovine model of mesenteric venous hypertension (MVH)by surgically occluding mesenteric veins for 3 days to investigate the functional and molecular adaptations of the mesenteric lymphatic vessels. The MVH model was characterized by an increase in mesenteric vein pressure from 10 to 30 mm Hg, a decrease in lymph protein concentration from 6 to 5 g/dL and an increase in intestinal water content from 72 to 78%. After 3‐days of MVH, isolated mesenteric lymphatic vessels demonstrated decreased contraction frequency, decreased ejection fraction and decreased stroke volume at each transmural pressure tested. Microarray analysis revealed that 117 genes were upregulated and 79 genes were down regulated in MVH lymphatics. A large number of the regulated genes are muscle contractile proteins, consistent with the changes in function. We further characterized changes in the mRNA of actin isoforms expressed in lymphatic muscle in response to venous hypertension. The smooth muscle actins (alpha and gamma) and skeletal actin were increased and cardiac actin decreased in lymphatics from the MHV model. Actin protein levels were analyzed by western blot analysis and revealed similar directional changes in response to MHV. These data suggest that lymphatic vessels undergo functional and molecular adaptation in response to changes in lymphdynamics in a time frame that may be important in resolution of edema. This work was supported by a LSI grant from Texas A&M University and CDC grant 623086.