Reduced number and impaired function of circulating endothelial progenitor cells in patients with abdominal aortic
Shih-Hsien Sung1, Tao-Cheng Wu, Jia-Shiong Chen
1Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan; Institute of Public Health, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Insights
The number and function of circulating endothelial progenitor cells (EPCs) are reduced in patients with abdominal aortic aneurysms (AAAs). Impaired EPCs suggest a potential role in AAA development and progression.
Area of Science:
- Vascular Biology
- Regenerative Medicine
- Cardiovascular Research
Background:
- Circulating endothelial progenitor cells (EPCs) are crucial for vascular repair and are linked to coronary artery disease (CAD).
- Abdominal aortic aneurysm (AAA) shares risk factors with CAD, but its relationship with EPCs is not well understood.
Purpose of the Study:
- To investigate the correlation between circulating EPCs and the presence and severity of AAA.
- To assess the functional capacity of EPCs in AAA patients.
Main Methods:
- Prospective enrollment of 78 subjects with suspected AAA.
- Evaluation of endothelial function using flow-mediated vasodilation (FMD).
- Quantification of circulating EPCs and colony-forming units (CFUs) via flow cytometry.
- Assessment of late outgrowth EPC function (proliferation, adhesion, migration, tube formation, senescence) in a subset of patients.
Main Results:
- AAA patients exhibited significantly lower FMD compared to controls.
- Reduced numbers of circulating EPCs (CD34+/KDR+, CD133+/KDR+) and CFUs were observed in AAA patients.
- EPC numbers (CFUs and CD34+/KDR+) were inversely correlated with AAA diameter.
- Impaired proliferation, adhesion, migration, tube formation, and increased senescence were noted in late outgrowth EPCs from AAA patients.
Conclusions:
- Both the number and function of EPCs are significantly impaired in patients with AAA.
- These findings suggest a potential role for EPC dysfunction in the pathogenesis of AAA.
Aim:
Circulating endothelial progenitor cells (EPCs) are associated with coronary artery disease (CAD) and predict its outcome. Although the pathophysiology of abdominal aortic aneurysm (AAA) is different, it shares some risk factors with CAD. Therefore, the correlation between EPCs and AAA was investigated.
Methods And Results:
Seventy-eight subjects (age 77.2 ± 7.8 years) with suspected AAA were prospectively enrolled. Cut-off values (men, 3.5-5.5 cm; women, 3-5 cm) were used to define normal aorta, small AAA, and large AAA on thoraco-abdominal computer tomography. Endothelial function was measured by flow-mediated vasodilation (FMD). Flow cytometry and colony-forming units (CFUs) were used to evaluate circulating EPC numbers. Circulating EPCs were defined as mononuclear cells with low CD45 staining and double-positive staining for KDR, CD34, or CD133. Late out-growth EPCs were cultured from six patients with large AAAs and six age- and sex-matched controls to evaluate proliferation, adhesion, migration, tube formation, and senescence. FMD was significantly lower with large (5.26% ± 3.11%) and small AAAs (6.31% ± 3.66%) than in controls (8.88% ± 4.83%, P=0.008). Both CFUs (normal 38.39 ± 12.99, small AAA 21.22 ± 7.14, large AAA 6.98 ± 1.97; P=0.026) and circulating EPCs (CD34(+)/KDR(+) and CD133(+)/KDR(+)) were significantly fewer in AAA patients than in controls. On multivariate analysis, CFUs and circulating EPCs (CD34(+)/KDR(+)) were independently, inversely correlated to AAA diameter. Proliferation, adhesion, migration, tube formation, and senescence of late EPCs were significantly impaired in AAA patients.
Conclusion:
The number and function of EPCs were impaired in AAA patients, suggesting their potential role in AAA.
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