Related Experiment Video
Updated: Aug 28, 2025
Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia
Published on: September 22, 2020
Circulating Biomarkers of Endothelial Dysfunction and Inflammation in Predicting Clinical Outcomes in Diabetic
Francesco Vieceli Dalla Sega1, Paolo Cimaglia1, Marco Manfrini1
1Maria Cecilia Hospital, GVM Care and Research, 48033 Cotignola, Italy.
Insights
Biomarkers like sICAM-1, endothelin-1, PAI-1, thrombomodulin, and sCD40L can predict outcomes in critical limb ischemia (CLI) patients with diabetes and diabetic foot ulcers (DFU). These markers help identify risks for poor healing and recurrence.
Area of Science:
- Vascular Biology and Medicine
- Diabetic Complications
- Biomarker Discovery
Background:
- Critical limb ischemia (CLI), a severe peripheral artery disease manifestation, often co-occurs with diabetes and non-healing diabetic foot ulcers (DFU).
- Standard treatments like percutaneous transluminal angioplasty (PTA) and surgery carry risks of post-procedure complications, including revascularization or further surgery.
- Predictive factors for adverse events in treated CLI patients remain incompletely understood, necessitating biomarker identification.
Purpose of the Study:
- To identify circulating biomarkers that predict the clinical course and outcomes in diabetic patients suffering from CLI and DFU.
- To investigate the association between specific molecular markers and key endpoints such as DFU healing, need for revascularization, and lesion recurrence.
Main Methods:
- Circulating levels of 23 molecules (inflammation, endothelial dysfunction, platelet activation, thrombophilia) were measured in 92 CLI and DFU patients.
- Patients underwent percutaneous transluminal angioplasty (PTA) and foot surgery.
- Associations between biomarker levels and clinical endpoints (DFU healing, revascularization, new lesions/relapse) were analyzed.
Main Results:
- Soluble intercellular adhesion molecule-1 (sICAM-1) and endothelin-1 were inversely associated with diabetic foot ulcer (DFU) healing.
- Plasminogen activator inhibitor-1 (PAI-1) and endothelin-1 correlated with the need for new limb revascularization.
- Thrombomodulin and soluble CD40 ligand (sCD40L) levels were linked to new lesions or recurrence, forming a basis for a predictive decision tree.
Conclusions:
- Specific biomarkers, including sICAM-1, endothelin-1, PAI-1, thrombomodulin, and sCD40L, show significant associations with adverse outcomes in diabetic CLI patients.
- These identified biomarkers can potentially stratify patients into risk clusters for developing new lesions or recurrence after treatment.
- Further validation could lead to improved clinical decision-making and personalized management strategies for critical limb ischemia.
Abstract:
Critical limb ischemia (CLI) is a severe manifestation of peripheral artery disease characterized by ischemic pain, which is frequently associated with diabetes and non-healing lesions to inferior limbs. The clinical management of diabetic patients with CLI typically includes percutaneous transluminal angioplasty (PTA) to restore limb circulation and surgical treatment of diabetic foot ulcers (DFU). However, even after successful treatment, CLI patients are prone to post-procedure complications, which may lead to unplanned revascularization or foot surgery. Unfortunately, the factors predicting adverse events in treated CLI patients are only partially known. This study aimed to identify potential biomarkers that predict the disease course in diabetic patients with CLI. For this purpose, we measured the circulating levels of a panel of 23 molecules related to inflammation, endothelial dysfunction, platelet activation, and thrombophilia in 92 patients with CLI and DFU requiring PTA and foot surgery. We investigated whether these putative biomarkers were associated with the following clinical endpoints: (1) healing of the treated DFUs; (2) need for new revascularization of the limb; (3) appearance of new lesions or relapses after successful healing. We found that sICAM-1 and endothelin-1 are inversely associated with DFU healing and that PAI-1 and endothelin-1 are associated with the need for new revascularization. Moreover, we found that the levels of thrombomodulin and sCD40L are associated with new lesions or recurrence, and we show that the levels of these biomarkers could be used in a decision tree to assign patients to clusters with different risks of developing new lesions or recurrences.
Related Concept Videos
01:21Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:27Peripheral Artery Disease III: Interprofessional Care
01:27Atherosclerosis II: Clinical Manifestations and Diagnostic Tests
01:30Coronary Artery Disease I: Introduction