Department of Internal Medicine, Division of Cardiology, University hospital Rostock, Ernst Heydemann Str 6, Rostock, 18055, Germany.
J Transl Med. 2012 Jul 9;10:143. doi: 10.1186/1479-5876-10-143.
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).
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.
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.
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.
患有冠心病的患者骨髓来源的循环祖细胞(BM-CPCs)在数量和功能活性方面受损。然而,BM-CPCs 的功能活性与病变冠状动脉的数量之间的关系尚不清楚。我们分析了缺血性心脏病(IHD)患者外周血(PB)中 BM-CPCs 的功能活性与病变冠状动脉数量之间的关系。
通过迁移测定和集落形成单位测定,分析了 120 例冠状动脉 1 支病变(IHD1,n=40)、冠状动脉 2 支病变(IHD2,n=40)、冠状动脉 3 支病变(IHD3,n=40)和健康对照组(n=40)患者的 BM-CPCs 功能活性。除糖尿病(DM)外,IHD 组的心血管危险因素总数没有显著差异,而 DM 在 IHD3 组与 IHD2 和 IHD1 相比明显更高。
与对照组相比,IHD 患者的集落形成能力(CFU-E:p<0.001,CFU-GM:p<0.001)和对基质细胞衍生因子 1(SDF-1:p<0.001)以及血管内皮生长因子(VEGF:p<0.001)的迁移反应的 BM-CPCs 减少。与 IHD1(VEGF:p<0.01,SDF-1:p<0.001;CFU-E:p<0.001,CFU-GM:p<0.001)和 IHD2(VEGF:p=0.003,SDF-1:p=0.003;CFU-E:p=0.001,CFU-GM:p=0.001)相比,IHD3 患者的 BM-CPCs 功能活性明显受损。IHD2 患者与 IHD1 患者的 BM-CPCs 功能活性无显著差异(VEGF:p=0.8,SDF-1:p=0.9;CFU-E:p=0.1,CFU-GM:p=0.1)。有趣的是,DM 患者的血红蛋白 AIc(HbAIc)水平与 BM-CPCs 的功能活性呈负相关(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)。
IHD 患者 PB 中的 BM-CPCs 功能活性受损。这种损伤随着病变冠状动脉数量的增加而增加。此外,在 DM 合并 IHD 患者中,缺血组织中 BM-CPCs 的再生能力进一步下降。此外,监测 PB 中 BM-CPCs 的水平可能为 IHD 患者提供新的见解。