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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
CD34+CD140b+ cells and circulating CXCL12 correlate with the angiographically assessed severity of cardiac allograft
Andreas Schober1, Mihail Hristov, Sieglinde Kofler
1Medizinische Poliklinik Innenstadt, Kardiologie, University of Munich, Munich, Germany. aschober@ukaachen.de
Insights
Circulating smooth muscle progenitor cells (SPCs), not endothelial progenitor cells (EPCs), are linked to cardiac allograft vasculopathy (CAV) severity. Elevated SPCs and CXCL12 indicate their role in transplant arteriosclerosis.
Area of Science:
- Cardiovascular Research
- Transplantation Immunology
- Regenerative Medicine
Background:
- Cardiac allograft vasculopathy (CAV) is a major cause of heart transplant failure.
- Vascular progenitor cells, including endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SPCs), are implicated in vascular repair and disease.
- The role of progenitor cells in CAV pathogenesis remains unclear.
Purpose of the Study:
- To investigate the association between circulating SPCs and EPCs and the severity of CAV.
- To determine if plasma CXCL12 levels correlate with CAV and progenitor cell counts.
- To explore the influence of immunosuppressive regimens on SPCs and CXCL12 in heart transplant recipients.
Main Methods:
- Peripheral blood samples from 187 heart transplant recipients were analyzed for CD34(+)CD140b(+) SPCs and CD34(+)KDR(+) EPCs using flow cytometry.
- CAV severity was assessed by angiography and a standardized scoring system.
- Plasma CXCL12 levels were measured, and associations with CAV, progenitor cells, and immunosuppression were analyzed via multivariate regression.
Main Results:
- CAV was present in 44.7% of patients; 59 had mild and 25 had severe CAV.
- Circulating SPCs were significantly higher in CAV patients compared to controls, with a stepwise increase in moderate to severe CAV.
- SPCs were elevated in stented CAV patients, while EPC counts remained unchanged; plasma CXCL12 correlated with CAV severity and SPC counts.
Conclusions:
- Circulating SPCs, but not EPCs, are elevated in patients with CAV.
- Elevated SPCs and plasma CXCL12 concentrations suggest a significant role in transplant arteriosclerosis.
- Immunosuppressive drugs did not influence SPC or CXCL12 levels in this cohort.
Aims:
We sought to determine whether circulating vascular progenitor cells, such as endothelial progenitor cells (EPCs) or smooth muscle progenitor cells (SPCs), were associated with the severity of cardiac allograft vasculopathy (CAV).
Methods And Results:
CD34(+)CD140b(+) SPCs and CD34(+)KDR(+) EPCs were measured in the peripheral circulation of 187 adult heart transplant recipients by flow cytometry. Cardiac allograft vasculopathy was quantified by angiography using a CAV-specific scoring system. Cardiac allograft vasculopathy was present in 84 patients (44.7%) and was classified as mild in 59 and severe in 25 cases. Circulating SPCs were more frequently detectable in CAV patients than in patients without CAV. The number of CD34(+)CD140b(+) cells showed a stepwise increase in patients with moderate and severe CAV. Smooth muscle progenitor cell counts were higher in patients with coronary stent implant compared with unstented patients with CAV. In contrast, peripheral CD34(+)KDR(+) EPC counts were not changed in CAV patients. Plasma CXCL12 levels correlated with the degree of CAV and SPC counts. None of the different immunosuppressive drug regimes was related to the SPC count or the CXCL12 levels. A multivariate regression analysis revealed that the SPC count was independently associated with the presence of CAV.
Conclusion:
Circulating SPCs, but not EPCs, and plasma CXCL12 concentrations are elevated in CAV patients, indicating that they play prominent roles in transplant arteriosclerosis.