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Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
Characterisation of progenitor cells in human atherosclerotic vessels
Evelyn Torsney1, Kaushik Mandal, Alison Halliday
1Department of Cardiac and Vascular Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK. etorsney@sgul.ac.uk
Insights
Vascular progenitor cells are present in human atherosclerotic lesions, with increased numbers found in the adventitia of diseased arteries. These cells may contribute to the development of atherosclerosis.
Area of Science:
- Vascular Biology
- Atherosclerosis Research
- Stem Cell Biology
Background:
- Animal models indicate endothelial and smooth muscle progenitor cells drive atherosclerosis.
- The presence and role of progenitor cells in human atherosclerotic vessels remain uncharacterized.
Purpose of the Study:
- To investigate the existence and characteristics of vascular progenitor cells in human atherosclerotic arteries.
- To quantify progenitor cell presence in normal versus atherosclerotic human vessels.
Main Methods:
- Human arterial segments (internal mammary artery, aorta) from bypass surgery patients were analyzed.
- Immunofluorescence staining was employed to detect progenitor cell markers (CD34, Sca-1, c-kit, VEGFR2, CD133).
Main Results:
- Vascular progenitor cells were identified in neointimal lesions and adventitia of atherosclerotic arteries.
- A two- to three-fold increase in adventitial progenitor cells was observed in atherosclerotic vessels compared to controls.
- Increased frequency of VEGFR2-expressing cells was noted in atherosclerotic adventitia (p<0.05).
Conclusions:
- This study provides the first evidence of vascular progenitor cells within human atherosclerotic lesions.
- An elevated number of progenitor cells in the adventitia of human atherosclerotic vessels suggests a role in disease progression.
- These progenitor cells may serve as a source for smooth muscle cells, macrophages, and endothelial cells in atherosclerotic plaques.
Abstract:
Recent data from animal models has demonstrated that both endothelial and smooth muscle progenitor cells contribute to the development of atherosclerosis. However, no data exists concerning the presence of progenitor cells in human atherosclerotic vessels. In the present study, a range of normal and atherosclerotic human arteries were collected from patients undergoing coronary artery bypass surgery. Segments of internal mammary artery (normal controls), and segments of proximal ascending aorta with visible fatty streak were analysed. Immunofluorescence was used to detect a panel of progenitor cell markers. A small number of progenitor cells were identified within neointimal lesions and the adventitia with variable expression of CD34, stem cell antigen (Sca-1), c-kit and VEGF receptor 2 (VEGFR2) markers, but no CD133 expression. On average there was a two- to three-fold increase in progenitor cell number in the adventitia of atherosclerotic vessels compared with normal controls, with a significant difference (p<0.05) in the frequency of cells expressing VEGFR2. Thus, we have provided the first evidence that vascular progenitor cells exist within atherosclerotic lesions, and identified an increased number of progenitor cells in the adventitia of human atherosclerotic vessels. These cells might be a source for smooth muscle cells (SMCs), macrophages and endothelial cells (ECs) that form atherosclerotic lesions.
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