Circulating endothelial progenitor cells do not contribute to plaque endothelium in murine atherosclerosis
Mette K Hagensen1, Jeong Shim, Troels Thim
1MSc, Atherosclerosis Research Unit, Institute of Clinical Medicine and Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. mette.hagensen@ki.au.dk
Insights
Circulating endothelial progenitor cells (EPCs) rarely contribute to plaque endothelium in mice with atherosclerosis. This challenges the theory that EPCs are crucial for the development of this arterial disease.
Area of Science:
- Cardiovascular Biology
- Cell Biology
- Atherosclerosis Research
Background:
- Endothelial progenitor cells (EPCs) are proposed to aid arterial repair after injury.
- The role of circulating EPCs in atherosclerosis, a major arterial disease, remains unclear.
- This study investigates EPC contribution to plaque endothelium in a mouse model.
Purpose of the Study:
- To determine if circulating EPCs contribute to plaque endothelium during atherogenesis.
- To assess EPC involvement in reendothelialization after plaque disruption.
Main Methods:
- Utilized lethally irradiated apolipoprotein E-deficient (apoE(-/-)) mice reconstituted with enhanced green fluorescent protein (eGFP) transgenic bone marrow.
- Examined carotid artery plaques and mechanically disrupted plaques using high-resolution microscopy.
- Employed sex-mismatched transplants and Y chromosome tracking for cell origin analysis.
Main Results:
- Only 1 eGFP+ endothelial cell was identified among 4232 analyzed in atherosclerotic plaques.
- Similarly, only 1 eGFP+ endothelial cell was found among 3170 analyzed after plaque disruption.
- Cell tracking confirmed a very low contribution of circulating EPCs to plaque endothelium.
Conclusions:
- Circulating EPCs seldom contribute to plaque endothelium in apoE(-/-) mice.
- These findings question the established theory of EPCs' significant role in atherogenesis.
- The study suggests limited therapeutic potential for circulating EPCs in treating atherosclerosis.
Background:
It has been reported that circulating endothelial progenitor cells (EPCs) home to and differentiate into endothelial cells after various kinds of arterial injury. By inference, EPCs are also proposed to be important in the most important arterial disease, atherosclerosis, but the evidence for this theory is not clear. In the present study, we assessed the contribution of circulating EPCs to plaque endothelium in apolipoprotein E-deficient (apoE(-/-)) mice.
Methods And Results:
To investigate whether EPCs in the circulating blood are a source of plaque endothelial cells during atherogenesis, we examined plaques in lethally irradiated apoE(-/-) mice reconstituted with bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic apoE(-/-) mice and plaques induced in segments of common carotid artery transplanted from apoE(-/-) mice into eGFP(+)apoE(-/-) mice. Among 4232 endothelial cells identified by a cell-type-specific marker (von Willebrand factor) and analyzed by high-resolution microscopy, we found only 1 eGFP(+). Using the Y chromosome to track cells after sex-mismatched transplants yielded similar results. To investigate whether circulating EPCs are involved in plaque reendothelialization after plaque disruption and superimposed thrombosis, we produced mechanical plaque disruptions in carotid bifurcation plaques in old lethally irradiated apoE(-/-) mice reconstituted with eGFP(+)apoE(-/-) bone marrow cells and carotid bifurcation plaques transplanted from old apoE(-/-) mice into eGFP(+)apoE(-/-) mice. Only 1 eGFP(+) endothelial cell was found among 3170 analyzed.
Conclusions:
Circulating EPCs rarely, if ever, contribute to plaque endothelium in apoE(-/-) mice. These findings bring into question the prevailing theory that circulating EPCs play an important role in atherogenesis.
