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

Nikhlesh Singh, Sivareddy Kotla, Elena Dyukova, James G. Traylor, A. Wayne Orr, Jonathan Chernoff, Tony Marion, Rao Gadiparthi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Pak1 plays an important role in various cellular processes, including cell motility, polarity, survival and proliferation. To date, its role in atherogenesis has not been explored. Here we report the effect of Pak1 on atherogenesis using atherosclerosis-prone apolipoprotein E-deficient (ApoE -/-) mice as a model. Disruption of Pak1 in ApoE-/- mice results in reduced plaque burden, significantly attenuates circulating IL-6 and MCP-1 levels, limits the expression of adhesion molecules and diminishes the macrophage content in the aortic root of ApoE-/- mice. We also observed reduced oxidized LDL uptake and increased cholesterol efflux by macrophages and smooth muscle cells of ApoE-/- :Pak1 -/- mice as compared with ApoE-/- mice. In addition, we detect increased Pak1 phosphorylation in human atherosclerotic arteries, suggesting its role in human atherogenesis. Altogether, these results identify Pak1 as an important factor in the initiation and progression of atherogenesis.

Original languageEnglish (US)
Article number7450
JournalNature Communications
Volume6
DOIs
StatePublished - Jun 24 2015

Fingerprint

p21-Activated Kinases
arteriosclerosis
Apolipoproteins E
genes
mice
Atherosclerosis
Genes
macrophages
Macrophages
efflux
smooth muscle
muscle cells
Peptide Initiation Factors
Cell Polarity
phosphorylation
Phosphorylation
locomotion
cholesterol
arteries
muscles

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Disruption of p21-activated kinase 1 gene diminishes atherosclerosis in apolipoprotein E-deficient mice. / Singh, Nikhlesh; Kotla, Sivareddy; Dyukova, Elena; Traylor, James G.; Orr, A. Wayne; Chernoff, Jonathan; Marion, Tony; Gadiparthi, Rao.

In: Nature Communications, Vol. 6, 7450, 24.06.2015.

Research output: Contribution to journalArticle

Singh, Nikhlesh ; Kotla, Sivareddy ; Dyukova, Elena ; Traylor, James G. ; Orr, A. Wayne ; Chernoff, Jonathan ; Marion, Tony ; Gadiparthi, Rao. / Disruption of p21-activated kinase 1 gene diminishes atherosclerosis in apolipoprotein E-deficient mice. In: Nature Communications. 2015 ; Vol. 6.
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