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. 2012 Jul 9:10:143.
doi: 10.1186/1479-5876-10-143.

Correlation between the functional impairment of bone marrow-derived circulating progenitor cells and the extend of coronary artery disease

Ilkay Bozdag-Turan  1 , R Goekmen Turan, Lylia Paranskaya, Nicole S Arsoy, C Hakan Turan, Ibrahim Akin, Stephan Kische, Jasmin Ortak, H Schneider, S Ludovicy, Tina Hermann, Giuseppe D'Ancona, Serkan Durdu, A Ruchan Akar, Hueseyin Ince, Christoph A Nienaber
Affiliations

Correlation between the functional impairment of bone marrow-derived circulating progenitor cells and the extend of coronary artery disease

Ilkay Bozdag-Turan et al. J Transl Med. .

Abstract

Background: Bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with coronary heart disease are impaired with respect to number and functional activity. However, the relation between the functional activity of BM-CPCs and the number of diseased coronary arteries is yet not known. We analyzed the influence of the number of diseased coronary arteries on the functional activity of BM-CPCs in peripheral blood (PB) in patients with ischemic heart disease (IHD).

Methods: The functional activity of BM-CPCs was measured by migration assay and colony forming unit in 120 patients with coronary 1 vessel (IHD1, n = 40), coronary 2 vessel (IHD2, n = 40), coronary 3 vessel disease (IHD3, n = 40) and in a control group of healthy subjects (n = 40). There was no significant difference of the total number of cardiovascular risk factors between IHD groups, beside diabetes mellitus (DM), which was significantly higher in IHD3 group compared to IHD2 and IHD1.

Results: The colony-forming capacity (CFU-E: p < 0.001, CFU-GM: p < 0.001) and migratory response to stromal cell-derived factor 1 (SDF-1: p < 0.001) as well as vascular endothelial growth factor (VEGF: p < 0001) of BM-CPCs were reduced in the group of patients with IHD compared to control group. The functional activity of BM-CPCs was significantly impaired in patients with IHD3 as compared to IHD1 (VEGF: p < 0.01, SDF-1: p < 0.001; CFU-E: p < 0.001, CFU-GM: p < 0.001) and to IHD2 (VEGF: p = 0.003, SDF-1: p = 0.003; CFU-E: p = 0.001, CFU-GM: p = 0.001). No significant differences were observed in functional activity of BM-CPCs between patients with IHD2 and IHD1 (VEGF: p = 0.8, SDF-1: p = 0.9; CFU-E: p = 0.1, CFU-GM: p = 0.1). Interestingly, the levels of haemoglobin AIc (HbAIc) correlated inversely with the functional activity of BM-CPCs (VEGF: p < 0.001, r = -0.8 SDF-1: p < 0.001, r = -0.8; CFU-E: p = 0.001, r = -0.7, CFU-GM: p = 0.001, r = -0.6) in IHD patients with DM.

Conclusions: The functional activity of BM-CPCs in PB is impaired in patients with IHD. This impairment increases with the number of diseased coronary arteries. Moreover, the regenerative capacity of BM-CPCs in ischemic tissue further declines in IHD patients with DM. Furthermore, monitoring the level of BM-CPCs in PB may provide new insights in patients with IHD.

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Figures

Figure 1
Figure 1
A and B: The colony-forming capacity and migratory response to stromal cell-derived factor 1 as well as vascular endothelial growth factor of BM-CPCs were reduced in patients with IHD compared to control group.
Figure 2
Figure 2
A and B: The migratory -and colony forming capacities of BM-CPCs were significantly impaired in patients with IHD3 compared to IHD1 and IHD2. In contrast, there were no significant changes in functional activity of BM-CPCs between the patients with IHD2 and IHD1.
Figure 3
Figure 3
A and B: The migratory response to VEGF and SDF-1 correlates inverse to the level of HbA1c in patients with DM.
Figure 4
Figure 4
A and B: The colony forming capacitiy correlates inverse to the level of HbA1c in patients with DM.
Figure 5
Figure 5
A and B: The migration and colony forming capacities of BM-CPCs are significantly reduced in patients with HbA1c >7% compared to patients with HbA1c <7%.
See this image and copyright information in PMC

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