Related Experiment Video
Updated: Aug 17, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein
Vladimir R Babaev1, Patricia G Yancey, Sergey V Ryzhov
1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA. vladimir.babaev@vanderbilt.edu
Objective:
Peroxisome proliferator-activated receptor gamma (PPARgamma) is highly expressed in macrophage-derived foam cells of atherosclerotic lesions, and its expression may have a dramatic impact on atherosclerosis.
Methods And Results:
To investigate the contribution of macrophage PPARgamma expression on atherogenesis in vivo, we generated macrophage-specific PPARgamma knockout (MacPPARgammaKO) mice. C57BL/6 and low-density lipoprotein (LDL) receptor-deficient (LDLR(-/-)) mice were reconstituted with MacPPARgammaKO or wild-type marrow and challenged with an atherogenic diet. No differences were found in serum lipids between recipients reconstituted with MacPPARgammaKO and wild-type marrow. In contrast, both C57BL/6 and LDLR(-/-) mice transplanted with MacPPARgammaKO marrow had significantly larger atherosclerotic lesions than control recipients. In addition, MacPPARgammaKO-->LDLR(-/-) mice had higher numbers of macrophages in atherosclerotic lesions compared with controls. Peritoneal macrophages isolated from the MacPPARgammaKO mice had decreased uptake of oxidized but not acetylated LDL and showed no changes in either cholesterol efflux or inflammatory cytokine expression. Macrophages from MacPPARgammaKO mice had increased levels of migration and CC chemokine receptor 2 (CCR2) expression compared with wild-type macrophages.
Conclusions:
Thus, macrophage PPARgamma deficiency increases atherosclerosis under conditions of mild and severe hypercholesterolemia, indicating an antiatherogenic role for PPARgamma, which may be caused, at least in part, by modulation of CCR2 expression and monocyte recruitment.
Insights
Macrophage peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency exacerbates atherosclerosis. This suggests PPARgamma plays an antiatherogenic role, potentially by regulating CC chemokine receptor 2 (CCR2) and monocyte recruitment.
Area of Science:
- Cardiovascular Biology
- Immunology
- Metabolic Diseases
Background:
- Peroxisome proliferator-activated receptor gamma (PPARgamma) is highly expressed in macrophage foam cells within atherosclerotic lesions.
- PPARgamma's role in atherosclerosis development is not fully understood.
Purpose of the Study:
- To investigate the in vivo contribution of macrophage PPARgamma expression to atherogenesis.
- To determine the impact of macrophage-specific PPARgamma deficiency on lesion development and macrophage function.
Main Methods:
- Generated macrophage-specific PPARgamma knockout (MacPPARgammaKO) mice.
- Transplanted wild-type or MacPPARgammaKO bone marrow into C57BL/6 and LDL receptor-deficient (LDLR(-/-)) mice.
- Challenged recipient mice with an atherogenic diet and analyzed atherosclerotic lesion development and macrophage characteristics.
Main Results:
- Macrophage PPARgamma deficiency did not alter serum lipid levels.
- Mice with macrophage PPARgamma deficiency exhibited significantly larger atherosclerotic lesions.
- Macrophages from MacPPARgammaKO mice showed decreased oxidized LDL uptake, increased migration, and elevated CC chemokine receptor 2 (CCR2) expression.
Conclusions:
- Macrophage PPARgamma deficiency promotes atherosclerosis in both mild and severe hypercholesterolemia.
- PPARgamma has an antiatherogenic role in macrophages.
- This protective effect may be mediated by the modulation of CCR2 expression and subsequent monocyte recruitment.
