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Depletion and Reconstitution of Macrophages in Mice
08:50

Depletion and Reconstitution of Macrophages in Mice

Published on: August 1, 2012

40.5K

Everolimus depletes plaque macrophages, abolishes intraplaque neovascularization and improves survival in mice with

Ammar Kurdi1, Lynn Roth1, Bieke Van der Veken1

  • 1Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.

Vascular Pharmacology
|December 28, 2018
PubMed
Abstract

Insights

Everolimus, an mTOR inhibitor, stabilized atherosclerotic plaques and improved survival in mice. This study shows its potential in treating advanced atherosclerosis and cardiovascular complications.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Immunology

Background:

  • Mechanistic target of rapamycin (mTOR) inhibition is a promising strategy for halting atherosclerosis.
  • Pre-existing research indicates mTOR inhibitors are effective in animal models of atherosclerosis.

Purpose of the Study:

  • To evaluate the efficacy of the mTOR inhibitor everolimus in stabilizing pre-existing atherosclerotic plaques.
  • To determine if everolimus can prevent cardiovascular complications and improve survival in a mouse model of advanced atherosclerosis.

Main Methods:

  • ApoE-/-Fbn1C1039G+/- mice were fed a Western diet for 12 weeks.
  • Mice then received daily treatment with everolimus (1.5 mg/kg) or vehicle for 12 weeks while continuing the Western diet.

Main Results:

  • Everolimus treatment reduced circulating Ly6Chigh monocytes and plaque macrophages, indicating plaque stabilization.
  • Intraplaque neovascularization was abolished, and hypoxic brain damage was reduced.
  • Cardiac function improved, leading to significantly increased survival rates (100% in everolimus group vs. 67% in vehicle group).

Conclusions:

  • Everolimus administration enhances atherosclerotic plaque stability in mice.
  • The mTOR inhibitor effectively counters cardiovascular complications, including improved survival, even when treatment is initiated later in the disease course.
Keywords:
Advanced atherosclerosisBrain hypoxiaEverolimusIntraplaque neovascularizationmTOR inhibition

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