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Quantification of Atherosclerosis in Mice
06:59

Quantification of Atherosclerosis in Mice

Published on: June 12, 2019

Accelerated atherosclerosis in Apoe-/- mice heterozygous for the insulin receptor and the insulin receptor

Elena V Galkina1, Matthew Butcher, Susanna R Keller

  • 1Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501, USA. galkinev@evms.edu

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 27, 2011
PubMed
Abstract

Insights

Impaired insulin signaling accelerates atherosclerosis by affecting vascular function. This study used novel mouse models to show how insulin receptor defects contribute to cardiovascular disease progression.

Area of Science:

  • Cardiovascular Biology
  • Metabolic Disease Research
  • Atherosclerosis Pathogenesis

Background:

  • Prediabetic states are linked to faster atherosclerosis development.
  • Limited mouse models exist to study the connection between prediabetes and atherosclerosis.
  • Understanding insulin signaling's role in atherogenesis is crucial.

Purpose of the Study:

  • To investigate the specific role of impaired insulin receptor (Insr) and insulin receptor substrate-1 (Irs1) signaling in promoting atherosclerosis.
  • To establish and utilize a novel mouse model for studying insulin signaling defects in the context of atherosclerosis.

Main Methods:

  • Generated double heterozygous apolipoprotein (Apoe)-knockout mice with defects in Insr and Irs1 (Insr(+/-)Irs1(+/-)Apoe(-/-)).
  • Fed mice a Western diet for 15 weeks and analyzed plasma markers (insulin, glucose, lipids).
  • Assessed atherosclerotic lesion size, performed bone marrow transfers, and analyzed vascular function markers (phospho-eNOS, vasorelaxation, VCAM-1, phospho-ERK, smooth muscle cell proliferation).

Main Results:

  • Insr(+/-)Irs1(+/-)Apoe(-/-) mice exhibited elevated fasting insulin but normal glucose and lipid profiles.
  • Increased atherosclerotic lesions were observed in both male and female Insr(+/-)Irs1(+/-)Apoe(-/-) mice.
  • Non-hematopoietic cells with impaired insulin signaling accelerated atherosclerosis; vascular dysfunction (decreased phospho-eNOS, impaired vasorelaxation) and inflammation (elevated VCAM-1) were noted.

Conclusions:

  • Defective insulin signaling in non-hematopoietic cells contributes to accelerated atherosclerosis.
  • Impaired insulin signaling promotes vascular dysfunction and inflammation, driving atherogenesis.
  • This study provides a valuable model for investigating insulin resistance-related cardiovascular disease.

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