Related Experiment Video

Updated: Apr 8, 2026

Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
07:36

Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice

Published on: September 26, 2018

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Disruption of p21-activated kinase 1 gene diminishes atherosclerosis in apolipoprotein E-deficient mice

Nikhlesh K Singh1, Sivareddy Kotla1, Elena Dyukova1

  • 1Department of Physiology, University of Tennessee Health Science Center, 894 Union Avenue, Memphis, Tennessee 38163, USA.

Nature Communications
|June 25, 2015
PubMed

Insights

Pak1 disruption reduces atherosclerosis in mice by lowering inflammation and plaque burden. Increased Pak1 activity in human arteries suggests its role in disease development.

Area of Science:

  • Molecular biology
  • Cardiovascular research
  • Cellular signaling

Background:

  • Pak1 is crucial for cellular functions like motility and proliferation.
  • The role of Pak1 in atherogenesis remains unexplored.

Purpose of the Study:

  • To investigate the role of Pak1 in the development of atherosclerosis.
  • To determine the effect of Pak1 disruption on atherosclerosis progression in a mouse model.

Main Methods:

  • Utilized atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice.
  • Generated ApoE(-/-) mice with Pak1 disruption (ApoE(-/-):Pak1(-/-)).
  • Analyzed plaque burden, inflammatory markers (IL-6, MCP-1), adhesion molecules, macrophage content, and lipid metabolism.

Main Results:

  • Pak1 disruption in ApoE(-/-) mice significantly reduced plaque burden.
  • Circulating IL-6 and MCP-1 levels, adhesion molecule expression, and macrophage content were diminished.
  • Macrophages and smooth muscle cells showed reduced oxidized LDL uptake and increased cholesterol efflux.
  • Increased Pak1 phosphorylation was observed in human atherosclerotic arteries.

Conclusions:

  • Pak1 plays a significant role in the initiation and progression of atherosclerosis.
  • Targeting Pak1 may offer a therapeutic strategy for treating atherosclerosis.
  • Pak1 is implicated in human atherogenesis based on phosphorylation levels in diseased arteries.

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