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Updated: Jun 28, 2026

Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia
Published on: September 22, 2020
Improvement in systemic endothelial condition following amputation in patients with critical limb ischemia
D J Newton1, F Khan, G Kennedy
1Vascular Diseases Research Unit, The Institute of Cardiovascular Research, Ninewells Hospital and Medical School, Dundee, UK. d.j.newton@dundee.ac.uk
Insights
Amputating ischemic limbs in critical limb ischemia (CLI) patients significantly reduced markers of endothelial dysfunction, including vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). This suggests peripheral tissue removal improves systemic vascular health.
Area of Science:
- Vascular Biology
- Cardiovascular Disease
- Limb Ischemia Research
Background:
- Critical limb ischemia (CLI) patients often have co-existing coronary heart disease, leading to high mortality.
- Peripheral ischemic tissue may release toxins, worsening systemic endothelial function and atherosclerosis.
- Investigating the impact of removing ischemic tissue on endothelial markers is crucial.
Purpose of the Study:
- To determine if markers of endothelial function improve after amputation of an ischemic limb in CLI patients.
- To assess the systemic effects of peripheral ischemic tissue on vascular endothelium.
Main Methods:
- Measured blood levels of VEGF, homocysteine, endothelin-1, VCAM-1, E-selectin, thrombomodulin, and vWF in 40 CLI patients.
- Assessed peripheral microvascular function using iontophoresis.
- Repeated measurements 6 months post-amputation.
Main Results:
- Patients with CLI exhibited elevated levels of endothelial products.
- Six months after amputation, vascular endothelial growth factor (VEGF) decreased by 70% (P<0.01).
- Six months after amputation, von Willebrand factor (vWF) decreased by 40% (P<0.01).
Conclusions:
- Reduced VEGF and vWF levels post-amputation support the hypothesis of systemic effects from peripheral ischemic tissue.
- Peripheral ischemic tissue may contribute to the progression of coronary heart disease in CLI patients.
- Amputation may improve systemic vascular health by removing a source of endothelial toxins.
Aim:
Most patients with critical limb ischemia (CLI) have co-existing coronary heart disease, which is the main cause of their increased mortality. Peripheral ischemic tissue produces circulating toxic molecules, which may worsen endothelial function systemically and contribute to the general atherosclerotic process within the body. We looked at whether markers of endothelial function improve after amputation of the ischemic limb, when this potential source of toxins has been removed.
Methods:
We measured blood levels of vascular endothelial growth factor (VEGF), homocysteine, endothelin-1, vascular cell adhesion molecule-1, E-selectin, thrombomodulin and von Willebrand factor (vWF) in 40 patients with CLI. We also assessed peripheral microvascular function in forearm skin by measuring responses to iontophoresis of acetylcholine and sodium nitroprusside. The measurements were repeated 6 months after amputation.
Results:
We found abnormally high levels of endothelial products in the patients, and 6 months later VEGF and vWF had both reduced significantly from previous values (by 70% and 40%, respectively; P<0.01 in both cases).
Conclusion:
Improvements in these two markers after amputation are consistent with the hypothesis that peripheral ischemic tissue has a systemic effect on the vascular endothelium and may contribute to the progression of coronary heart disease in patients with CLI.
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