Angiogenesis,Lymphangiogenesis,and Inflammation

In the binary world of vascular biology, it seems that investigators focus either upon angiogenesis or lymphangiogenesis, but rarely both. Nevertheless, it is generally acknowledged that both processes play an important mechanistic role in the pathogenesis and propagation of the inflammatory response.^1,2 Further insights into the relationships that link these two processes might be predicted to provide both theoretical and, potentially, pragmatic benefits.

In the current issue of Lymphatic Research and Biology, Sweat et al. provide the results of their investigations into the relationships between lymphangiogenesis and angiogenesis during inflammation in rat mesentery microvascular networks. ³ Since the two vasculatures play a coordinated role in the regulation of interstitial fluid balance and immune cell trafficking, their objective was to characterize the temporal and spatial relationships in the growth of lymphatic and blood vessels of the adult rat mesentery following an inflammatory stimulus.

In this study, rat mesentery was harvested at defined time points after an inflammatory stimulus and immunolabeled for PECAM, LYVE-1, Prox1, podoplanin, CD11b, and class III β-tubulin. Quantitative analysis reveals that angiogenesis distinctly proceeds angiogenesis. The appearance of lymphangiogenesis correlates with the upregulation of class III β-tubulin expression by endothelial cells along lymphatic blind-ended vessels and with increased lymphatic/blood endothelial cell connections. Interestingly, the presence of lymphatics attenuated blood capillary sprouting. This study supports the observations that the lymphatic/blood endothelial cell connections can be influenced by their local environment, and that, in a time-dependent manner, lymphatic endothelial cells undergo phenotypic changes during microvascular network growth.

Among the implications of these fascinating observations, one can conclude that the physical interactions among lymphatic and blood vasculatures are dynamic and complex. The authors suggest that the tissues studied in this investigation might be employed more generally to investigate the signaling molecules involved in lymphatic/blood system mispatterning.