Differential regulation of lymphatic junctional morphology and the potential effects on cardiovascular diseases

Figures

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  FIGURE 1. Lymphatic junctional morphology during health and inflammation. In a healthy lymphatic vessel (left), the initial lymphatics are lined with button junctions. As interstitial pressure increases, the anchoring filaments expand with the extracellular matrix which facilitates lymph entry through the gaps between buttons. Lymph is maintained within the lymphatic system by virtue of the zipper junctions in the collecting lymphatics. During inflammation (right), initial lymphatics undergo a button-to-zipper transformation which may prevent lymph uptake. Less is known about the junctional morphology of collecting lymphatics during inflammation, but some studies suggest zipper-to-button transformation which would cause leakage of any lymph that makes it into the system. Overall, this contributes to poor lymphatic flux during inflammation.

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  FIGURE 2. Current knowledge of molecular mechanisms regulating lymphatic button and zipper formation. Angpt2 has been found to affect both button and zipper formation. For button formation (left), Angpt2 activates Tie2 receptors on LECs, leading to its phosphorylation and activation of PI3K, AKT, eNOS, and eventually phosphorylation of VE-cadherin. For zipper formation (right), Angpt2 becomes dephosphorylated by unknown mechanisms. However, VEGF-A has been shown to induce zippering in the skin and intestine, but not the lungs. Adrenomedullin also contributes to zipper formation.