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Vascular endothelial cadherin (VE-cadherin) is crucial for cardiac lymphatic development and maintenance. Its loss disrupts lymphatic signaling but preserves cardiac function after injury.

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Area of Science:

  • Cardiovascular Biology
  • Lymphatic System Development
  • Molecular Signaling

Background:

  • Vascular endothelial cadherin (VE-cadherin) plays varied roles in lymphatic vessels.
  • Its specific function in cardiac lymphatics and interaction with lymphangiogenic factors requires further investigation.

Purpose of the Study:

  • To determine the spatiotemporal functions of VE-cadherin in cardiac lymphatics.
  • To elucidate how VE-cadherin loss impacts prolymphangiogenic signaling pathways, including adrenomedullin and VEGF-C/VEGFR3.

Main Methods:

  • Utilized conditional knockout mice (Cdh5;Prox1CreER) to delete VE-cadherin in lymphatic endothelial cells across different life stages.
  • Assessed lymphatic architecture and function via immunostaining and lymphangiography.
  • Evaluated cardiac function post-myocardial infarction and analyzed cellular signaling pathways through in vitro knockdown experiments.

Main Results:

  • Embryonic VE-cadherin deletion led to dilated cardiac lymphatics with altered morphology.
  • Postnatal deletion caused lymphatic disassembly, while adult deletion resulted in regression of the epicardial lymphatic network and impaired lymphatic function.
  • Surprisingly, VE-cadherin deletion did not compromise cardiac function at baseline or after myocardial infarction.
  • Mechanistically, VE-cadherin loss caused VEGFR3 internalization, impairing VEGF-C and adrenomedullin signaling and downstream proliferation.

Conclusions:

  • VE-cadherin is essential for cardiac lymphatic development and maintenance by stabilizing prolymphangiogenic signaling nodes.
  • Despite its role in lymphatic integrity, VE-cadherin is not required for basal or injury-induced cardiac function.