Abstract
Exercise mobilizes angiogenic cells, which stimulate vascular repair. However, limited research suggests exercise-induced increase of endothelial progenitor cell (EPCs) is completely lacking in type 1 diabetes (T1D). Clarification, along with investigating how T1D influences exercise-induced increases of other angiogenic cells (hematopoietic progenitor cells; HPCs) and cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), is needed. Thirty T1D patients and 30 matched non-diabetes controls completed 45 min of incline walking. Circulating HPCs (CD34+, CD34+CD45dim) and EPCs (CD34+VEGFR2+, CD34+CD45dimVEGFR2+), and subsequent expression of CXCR4 and CXCR7, were enumerated by flow cytometry at rest and post-exercise. Counts of HPCs, EPCs and expression of CXCR4 and CXCR7 were significantly lower at rest in the T1D group. In both groups, exercise increased circulating angiogenic cells. However, increases was largely attenuated in the T1D group, up to 55% lower, with CD34+ (331 ± 437 Δcells/mL vs. 734 ± 876 Δcells/mL p = 0.048), CD34+VEGFR2+ (171 ± 342 Δcells/mL vs. 303 ± 267 Δcells/mL, p = 0.006) and CD34+VEGFR2+CXCR4+ (126 ± 242 Δcells/mL vs. 218 ± 217 Δcells/mL, p = 0.040) significantly lower. Exercise-induced increases of angiogenic cells is possible in T1D patients, albeit attenuated compared to controls. Decreased mobilization likely results in reduced migration to, and repair of, vascular damage, potentially limiting the cardiovascular benefits of exercise.Trial registration: ISRCTN63739203.
Highlights
Abbreviations cardiovascular diseases (CVD) Cardiovascular diseases cell surface expression of chemokine receptor 4 (CXCR4) Chemokine receptor 4 CXCR7 Chemokine receptor 7 EPCs Endothelial progenitor cells haematopoietic stem/progenitor cells (HPC) Haematopoietic progenitor cells CRF Newcastle NIHR Clinical Research Facility
In combination with hyperglycemia and glucose fluctuations, it is possible that dysfunctional HPCs and EPCs contribute to increased vascular d amage[15,16] and progression of micro and macrovascular c omplications[17], with individuals with type 1 diabetes having a two- to eightfold increase in mortality rates compared with the general population largely due to cardiovascular diseases (CVD)[18,19,20]
Within other chronic diseases, diminished number of C D34+CXCR4+ cells may be a better predictor of mortality than CD34+ cells a lone[9], while the expression of CXCR7 has been linked to cell survival in diabetic condition in vitro, limited evidence exists in human s tudies[30]
Summary
Abbreviations CVD Cardiovascular diseases CXCR4 Chemokine receptor 4 CXCR7 Chemokine receptor 7 EPCs Endothelial progenitor cells HPCs Haematopoietic progenitor cells CRF Newcastle NIHR Clinical Research Facility. Endothelial progenitor cells (EPCs), first discovered in 1997, are mononuclear cells which have the potential to stimulate vascular repair[1] Evidence demonstrates that these cells can differentiate into endothelial cells in vitro[1,2], incorporate into sites of angiogenesis in vivo[3,4] and exert proangiogenic abilities via paracrine a ction[2]. In combination with hyperglycemia and glucose fluctuations, it is possible that dysfunctional HPCs and EPCs contribute to increased vascular d amage[15,16] and progression of micro and macrovascular c omplications[17], with individuals with type 1 diabetes having a two- to eightfold increase in mortality rates compared with the general population largely due to cardiovascular diseases (CVD)[18,19,20]. Within other chronic diseases, diminished number of C D34+CXCR4+ cells may be a better predictor of mortality than CD34+ cells a lone[9], while the expression of CXCR7 has been linked to cell survival in diabetic condition in vitro, limited evidence exists in human s tudies[30]
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