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Updated: May 17, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Bone marrow endothelial progenitors augment atherosclerotic plaque regression in a mouse model of plasma lipid
Longbiao Yao1, Janet Heuser-Baker, Oana Herlea-Pana
1Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Insights
Endothelial progenitor cells (EPCs) aid in vascular repair. This study shows that boosting EPCs can improve plaque regression in atherosclerosis, suggesting cell therapy combined with statins for treatment.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Vascular Biology
Background:
- Atherosclerosis initiation involves hypercholesterolemia-induced endothelial damage.
- Endothelial progenitor cells (EPCs) are crucial for vascular repair and regeneration.
- The role of EPCs in atherosclerosis regression remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of EPCs in promoting atherosclerosis plaque regression.
- To determine if augmenting EPC levels can enhance regression of existing atherosclerotic plaques.
Main Methods:
- Utilized a Reversa mouse model with reversible hypercholesterolemia.
- Adoptive transfer of green fluorescent protein (GFP)-labeled EPCs (Tie2-GFP(+)) into atheroregressing mice.
- Administered AMD3100, a stem cell mobilizer, to assess its effect on plaque regression.
Main Results:
- Reversal of hypercholesterolemia partially reduced atherosclerotic burden but did not achieve complete plaque regression.
- Adoptive transfer of EPCs significantly augmented plaque regression.
- Engraftment of transferred EPCs correlated with increased nitric oxide production and improved vascular relaxation.
- AMD3100 treatment also enhanced plaque regression by mobilizing EPCs.
Conclusions:
- Partial atherosclerosis plaque regression occurs with hypercholesterolemia normalization.
- EPCs play a pivotal role in augmenting atherosclerosis regression.
- Cell therapy or stem cell mobilization strategies, potentially combined with statins, show promise for treating atherosclerosis.
Abstract:
The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings of endothelial damage, endothelial progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites of vascular injury where they aid endothelial regeneration. Given the beneficial effects of EPCs in vascular repair, we hypothesized that these cells play a pivotal role in atherosclerosis regression. We tested our hypothesis in the atherosclerosis-prone mouse model in which hypercholesterolemia, one of the main factors affecting EPC homeostasis, is reversible (Reversa mice). In these mice, normalization of plasma lipids decreased atherosclerotic burden; however, plaque regression was incomplete. To explore whether endothelial progenitors contribute to atherosclerosis regression, bone marrow EPCs from a transgenic strain expressing green fluorescent protein (GFP) under the control of endothelial cell-specific Tie2 promoter (Tie2-GFP(+)) were isolated. These cells were then adoptively transferred into atheroregressing Reversa recipients where they augmented plaque regression induced by reversal of hypercholesterolemia. Advanced plaque regression correlated with engraftment of Tie2-GFP(+) EPCs into endothelium and resulted in an increase in atheroprotective nitric oxide and improved vascular relaxation. Similarly augmented plaque regression was also detected in regressing Reversa mice treated with the stem cell mobilizer AMD3100 which also mobilizes EPCs to peripheral blood. We conclude that correction of hypercholesterolemia in Reversa mice leads to partial plaque regression that can be augmented by AMD3100 treatment or by adoptive transfer of EPCs. This suggests that direct cell therapy or indirect progenitor cell mobilization therapy may be used in combination with statins to treat atherosclerosis.
