Abstract
The design of therapies aimed at manipulating microvascular growth requires understanding the relationships between angiogenesis and lymphangiogenesis. A critical question remains whether blood and lymphatic vessels can switch their identity in adult tissues. Lysophosphatidic acid (LPA), a lipid linked to oncogenesis, wound healing, and inflammation, has been shown to upregulate lymphatic marker expression by HUVECs in vitro. The objective of this study was to determine if LPA stimulation induces blood to lymphatic vessel phenotypic transition in intact microvascular networks. Using the rat mesentery culture model, which enables ex vivo investigation of angiogenesis and lymphangiogenesis, tissues from adult male Wistar rats were cultured for 3 days in serum‐free minimum essential media (MEM) or MEM with LPA (20 µM). Tissues were labeled for PECAM and either LYVE‐1, Prox1, or podoplanin to identify blood and lymphatic vessels, respectively. LPA stimulation caused a significant increase in blood capillary sprouting indicative of angiogenesis. Observation of LYVE‐1+ filopodia extensions suggests LPA stimulation also causes lymphangiogenesis. However, no indication of blood‐to‐lymphatic phenotype transition was observed. Blood vessels identified based on morphology and PECAM labeling intensity lacked lymphatic marker expression. These results indicate LPA stimulation is not sufficient to induce a lymphatic phenotype in blood vessels of intact microvascular networks. This emphasizes the importance of investigating lymphatic/blood vessel relationships in real microvascular network versus cell culture scenarios and motivates new questions regarding the mechanisms that maintain vessel identity.
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