Migratory activity of circulating progenitor cells and serum SDF-1α predict adverse events in patients with myocardial infarction
Orazio Fortunato1, Gaia Spinetti, Claudia Specchia
1IRCCS MultiMedica, Milan, Italy.
Insights
Reduced migratory activity of circulating progenitor cells (PCs) and elevated SDF-1α levels after acute myocardial infarction (AMI) predict adverse clinical outcomes, including death and heart failure.
Area of Science:
- Cardiovascular Medicine
- Regenerative Medicine
- Biomarker Discovery
Background:
- Pro-angiogenic progenitor cells (PCs) mobilize from bone marrow to ischemic sites post-acute myocardial infarction (AMI).
- The predictive value of early circulating PC characteristics for long-term outcomes in AMI patients remains unclear.
Purpose of the Study:
- To investigate if the number and migratory activity of circulating progenitor cells (PCs) can predict adverse clinical events in patients following AMI.
- To assess the role of serum cytokine levels, specifically SDF-1α, in conjunction with PC activity.
Main Methods:
- Assessed basal counts and in vitro migratory activity of CD34+/CD45+/CD133+/CXCR4+ PCs and serum cytokine levels in 172 AMI patients within 5 days of infarction.
- Utilized multivariable regression models to analyze the association between PC counts, cytokine levels, and 1-year clinical outcomes (death, repeat AMI, new-onset heart failure).
Main Results:
- Patients experiencing adverse events had higher serum SDF-1α levels and reduced spontaneous PC motility compared to event-free subjects.
- The percentage of non-migrated PCs (towards vehicle or SDF-1α) independently predicted death/repeat AMI (OR=2) and new-onset heart failure (OR=1.90).
- Elevated serum SDF-1α levels were also a significant predictor of adverse events (OR=3.8).
Conclusions:
- Biomarkers reflecting the migratory capacity of circulating progenitor cells (PCs) can aid in assessing secondary risk in acute myocardial infarction (AMI) patients.
- These findings suggest that impaired PC function and elevated SDF-1α are potential indicators of poor prognosis post-AMI.
Aims:
Following acute myocardial infarction (AMI), pro-angiogenic progenitor cells (PCs) are released from the bone marrow into the circulation and home to the ischaemic site attracted by a chemokine gradient. It is unknown if components of this early homeostatic response might help forecast the long-term clinical outcome. This study investigates if the number and migratory activity of circulating PCs predict adverse events in patients with AMI (clinical trial: NCT01271309).
Methods And Results:
Basal counts and in vitro migratory activity of CD34/CD45/CD133/CXCR4 PCs and serum cytokine levels were assessed during the first 5 days after AMI in a consecutive series of 172 patients. Clinical outcomes of the study were death, repeat AMI, and new-onset heart failure at a 1-year follow-up. The association between PC counts and cytokine levels with the incidence of clinical outcomes was assessed by multivariable regression models. AMI patients who underwent an event showed higher serum stromal cell-derived factor 1α (SDF-1α) levels and reduced spontaneous motility of PCs in an in vitro migration assay when compared with event-free subjects. After adjustment for age, gender, the presence or absence of ST elevation, or diabetes, the percentage of PCs non-migrated towards vehicle or SDF-1α were both independent predictors of death or repeat AMI and new-onset heart failure (odds ratio [OR] = 2, P = 0.015 and OR = 1.90, P = 0.018, respectively). Moreover, serum SDF-1α levels predict adverse events (OR = 3.8, P = 0.007).
Conclusion:
Biomarkers reflecting the migratory activity of circulating PCs may aid the assessment of secondary risk in AMI patients.
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