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Updated: Jun 19, 2026

Quantification of Atherosclerosis in Mice
06:59

Quantification of Atherosclerosis in Mice

Published on: June 12, 2019

Beta2 integrins modulate the initiation and progression of atherosclerosis in low-density lipoprotein receptor

Aksam Merched1, Katherine Tollefson, Lawrence Chan

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, R630, Houston, TX 77030, USA. amerched@bcm.edu

Cardiovascular Research
|October 22, 2009
PubMed
Abstract

Insights

Beta2 integrins initially protect against atherosclerosis, but later accelerate its progression. This study used timed bone marrow transplantation in mice to show beta2 integrin

Area of Science:

  • Cardiovascular Research
  • Immunology
  • Atherosclerosis Research

Background:

  • Beta2 integrin-mediated adhesion is crucial in cardiovascular disease, yet clinical trials targeting these molecules have yielded disappointing results.
  • Understanding the dynamic role of beta2 integrins in atherosclerosis progression is essential for developing effective therapies.

Purpose of the Study:

  • To investigate the stage-dependent effects of beta2 integrin inactivation on atherosclerosis development.
  • To elucidate the mechanisms by which beta2 integrins influence macrophage function in the context of atherosclerosis.

Main Methods:

  • Timed bone marrow transplantation (BMT) of CD18(-/-) cells into low-density lipoprotein receptor knockout (LDLR(-/-)) mice at different stages of atherosclerosis.
  • Analysis of atherosclerotic lesion progression and macrophage function (LDL uptake, phagocytosis).
  • Gene expression profiling of CD18(-/-) and CD18(+/+) macrophages.

Main Results:

  • Early BMT before fatty streak formation showed a short-term protective effect (34% lesion reduction).
  • Beta2 integrin inactivation did not affect lesion progression once fatty streaks had developed.
  • BMT with CD18(+/+) cells enhanced lesion progression in mature lesions, while CD18(-/-) BMT did not.
  • Beta2 integrins modulated macrophage uptake of LDL and phagocytosis of apoptotic cells via MAPK signaling.

Conclusions:

  • Beta2 integrin-mediated leukocyte-vessel wall interaction is time-dependent and dynamic.
  • During initiation, beta2 integrins protect against atherosclerotic lesion formation.
  • In later stages with chronic dyslipidemia, beta2 integrins exert a pro-atherogenic effect, accelerating disease progression.

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