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Published on: October 17, 2017
Migratory activity of circulating mononuclear cells is associated with cardiovascular mortality in type 2 diabetic
Gaia Spinetti1, Claudia Specchia, Orazio Fortunato
1Corresponding author: Paolo Madeddu, paolo.madeddu@bristol.ac.uk.
Insights
Increased migratory activity of specific mononuclear cells (CD45dimCD34posCXCR4posKDRpos) predicts cardiovascular death in type 2 diabetic patients with critical limb ischemia. This finding may help identify high-risk individuals needing closer monitoring and tailored treatments.
Area of Science:
- Cardiovascular Medicine
- Diabetology
- Cell Biology
Background:
- Predicting clinical outcomes for diabetic patients with critical limb ischemia (CLI) remains challenging.
- Circulating mononuclear cells, specifically CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells, are investigated for their prognostic potential.
Purpose of the Study:
- To determine if the abundance and migratory activity of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells can predict major amputation and cardiovascular death in type 2 diabetic patients with CLI undergoing angioplasty.
- To identify novel biomarkers for risk stratification in this patient population.
Main Methods:
- A prospective study of 119 type 2 diabetic patients with CLI.
- Assessment of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells by flow cytometry and in vitro migration assays.
- Multivariable regression analysis to evaluate the association between cell characteristics and clinical events at 18-month follow-up.
Main Results:
- No association was found between cell counts or migratory activity and amputation risk.
- Higher in vitro migration of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells was significantly associated with cardiovascular death (P = 0.0095).
- Cell migration independently predicted cardiovascular mortality, with a doubling of migrated cells increasing hazard by 100% (P < 0.0001).
Conclusions:
- In vitro migratory activity of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells is a potent predictor of cardiovascular mortality in type 2 diabetic patients with CLI.
- This finding offers a new biomarker for identifying high-risk patients who may benefit from specialized diagnostic and therapeutic interventions post-revascularization.
Objective:
Prediction of clinical outcome in diabetic patients with critical limb ischemia (CLI) is unsatisfactory. This prospective study investigates if the abundance and migratory activity of a subpopulation of circulating mononuclear cells, namely, CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells, predict major amputation and cardiovascular death in type 2 diabetic patients undergoing percutaneous transluminal angioplasty for CLI.
Research Design And Methods:
A consecutive series of 119 type 2 diabetic patients with CLI was enrolled. CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells were assessed by flow cytometry upon isolation and also after spontaneous or stromal cell-derived factor 1α-directed migration in an in vitro assay. The association between basal cell counts and migratory activity and the risk of an event at 18-month follow-up was evaluated in a multivariable regression analysis.
Results:
Time-to-event analysis of amputation (n = 13) showed no association with the candidate predictors. Sixteen cardiovascular deaths occurred during 18 months of follow-up. Abundance of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells was not associated with cardiovascular mortality. Interestingly, in vitro migration of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells was higher in patients with cardiovascular death compared with event-free subjects (percentage of migrated cells median value and interquartile range, 0.03 [0.02-0.07] vs. 0.01 [0.01-0.03]; P = 0.0095). Multivariable regression model analysis showed that cell migration forecasts cardiovascular mortality independently of other validated predictors, such as age, diagnosed coronary artery disease, serum C-reactive protein, and estimated glomerular filtration rate. In this model, doubling of migrated cell counts increases the cardiovascular death hazard by 100% (P < 0.0001).
Conclusions:
The new predictor could aid in the identification of high-risk patients with type 2 diabetes requiring special diagnostic and therapeutic care after revascularization.
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