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Related Experiment Video

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LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
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Effects of LDL Receptor Modulation on Lymphatic Function.

Andreea Milasan1,2, François Dallaire2, Gaétan Mayer3,4

  • 1Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.

Scientific Reports
|June 10, 2016
PubMed
Summary
This summary is machine-generated.

Atherosclerosis impairs lymphatic vessel function early, linked to cholesterol transport via LDLR. PCSK9 influences lymphatic function, offering new therapeutic targets for atherosclerosis.

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Area of Science:

  • Cardiovascular Biology
  • Lymphatic Physiology
  • Atherosclerosis Pathogenesis

Background:

  • Atherosclerosis involves immune cell and cholesterol buildup in arteries.
  • Lymphatic vessels are crucial for macrophage reverse cholesterol transport, but mechanisms are unclear.
  • Early lymphatic dysfunction may precede atherosclerotic lesion development.

Purpose of the Study:

  • To investigate the physiological and temporal origins of lymphatic dysfunction in atherosclerosis.
  • To characterize the role of LDLR and PCSK9 in atherosclerosis-associated lymphatic impairment.
  • To identify potential therapeutic targets for atherosclerosis by studying lymphatic function.

Main Methods:

  • Assessed collecting lymphatic vessel function in Pcsk9(-/-) and WT mice.
  • Evaluated lymphatic function in Ldlr(-/-); hApoB100(+/+) mice before lesion formation.
  • Investigated the effect of a VEGFR-3 agonist on lymphatic dysfunction.

Main Results:

  • Pcsk9(-/-) mice showed improved lymphatic vessel function and increased LDLR expression.
  • Lymphatic dysfunction was observed early in atherosclerosis-prone mice, independent of cholesterol but dependent on LDLR.
  • VEGFR-3 agonist treatment ameliorated the early lymphatic impairment.

Conclusions:

  • LDLR modulation is linked to early lymphatic dysfunction in atherosclerosis.
  • PCSK9 plays a multifaceted role in lymphatic function.
  • Targeting LDLR and PCSK9 presents potential therapeutic strategies for atherosclerosis prevention and treatment.