Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. This study investigated the relationship between circulating EPCs and high-sensitivity C-reactive protein (hs-CRP) in patients with diabetes.
Methods
Our study population comprised 190 consecutive patients, with and without diabetes. To obtain EPC numbers, CD34+ and CD133+ cells in peripheral blood were counted by flow cytometry.
Results
Significantly higher hs-CRP levels were observed in patients with diabetes than in those without diabetes. However, the number of EPCs was significantly lower in diabetic patients and in patients with high hs-CRP levels. Patients with diabetes and high hs-CRP levels showed a marked decrease in the number of EPCs compared with non-diabetic patients with low hs-CRP levels.
Conclusion
These results suggest that inflammation leads to decreased circulating EPCs in patients with diabetes, which might be related to the pathogenesis of diabetic vascular disease.
Hubacek J., Verma S., Shewchuk L. et al. Rationale and design of the Glitazones and the Endothelium (GATE) study: evaluation of rosiglitzone on endothelial function in patients with diabetes. Can J Cardiol2004;20:1449-53.
2.
Tepper OM, Galiano RD, Capla JM et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures . Circulation2002;106:2781-6.
3.
Tateishi-Yuyama E., Matsubara H., Murohara T. et al. Therapeutic angiogenesis for patients with critical limb ischemia using autologous bone marrow cell transplantation: a randomized, multicenter, controlled trial. Lancet2002;360:427-35.
4.
Tachi Y., Fukui D., Wada Y. et al. Changes in angiogenesis-related factors in serum following autologous bone marrow cell implantation for severe limb ischemia. Expert Opin Biol Ther2008;8:705-12.
5.
Peichev M., Naiyer AJ, Pereira D. et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood2000;95:952-8.
6.
Vasa M., Fichtlscherer S., Aicher A. et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res2001;89:E1-7.
7.
Hill JM, Zalos G., Halcox JP et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med2003;348:593-600.
8.
Eizawa T., Ikeda U., Murakami Y. et al. Decrease in circulating endothelial progenitor cells in patients with stable coronary artery disease. Heart2004;90:685-6.
9.
Tepper OM, Galiano RD, Capla JM et al. Human endothelial progenitor cells from type II diabetic exhibit impaired proliferation, adhesion, and incorporation into vascular structures . Circulation2002; 106:2781-6.
10.
Ridker PM, Hennekens CH, Buring JE et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med2000;342:836-43.
11.
Verma S., Wang CH, Li SH et al. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation2002;106:913-9.
12.
Devaraj S., Xu DY, Jiala I.C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells. Circulation2003;107:398-04.
13.
Verma S., Kuliszewski MA, Li SH et al. C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function. Circulation2004;109:2058-67.
14.
Hayaishi-Okano R., Yamasaki Y., Katakami N. et al. Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes . Diabetes Care2002 ;25:1432-8.
15.
Eizawa T., Murakami Y., Matsui K. et al. Circulating endothelial progenitor cells are reduced in hemodialysis patients. Curr Med Res Opin2003;19:627-33.
16.
Khan SS, Solomon MA, McCoy JP Jr.Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry B Clin Cytom2005;64:1-8.
17.
Loomans CJ, de Koning EJ, Staal FJ et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes2004;53:195-9.
18.
Bahlmann FH , de Groot K., Mueller O. et al. Stimulation of endothelial progenitor cells: A new putative therapeutic effect of angiotensin II receptor antagonists . Hypertension2005 ;45:526-9.
19.
Kusuyama T. , Omura T., Nishiya D. et al. Effects of treatment for diabetes mellitus on circulating vascular progenitor cells. J Pharmacol Sci2006;102:96-102.
20.
Fadini GP, Sartore S., Albiero M. et al. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol2006;26:2140-6.
21.
Fanini GP, Agostini C., Sartore S. et al. Significance of endothelial progenitor cells in subjects with diabetes . Diabetes Care2007; 30:1305-13.
22.
Krankel N., Adams V., Linke A. et al. Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arterioscler Thromb Vasc Biol2005;25:698-703.
23.
Humpert PM, Neuwirth R., Battista MJ et al. SDF-1 genotype influences insulin-dependent mobilization of adult progenitor cells in type 2 diabetes. Diabetes Care2005;28:934-6.
24.
Brownlee M.The pathobiology of diabetic complications: a unified mechanism. Diabetes2005;54:1615-25.
25.
Sorrentino SA, Bahlmann FH, Besler C. et al. Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus. Circulation2007;116:163-73.
26.
Fujii H., Li S., Szmitko P. et al. C-reactive protein alters antioxidant defenses and promotes apoptosis in endothelial progenitor cells. Arterioscler Thromb Vasc Biol2006;26:2476-82.
27.
Suh W., Kim KL, Choi JH et al. C-reactive protein impairs angiogenic functions and decreases the secretion of arteriogenic chemo-cytokines in human endothelial progenitor cells. Biochem Biophys Res Commun2004;321:65-71.
28.
Schillinger M., Exner M., Amighi J. et al. Joint effects of C-reactive protein and glycated hemoglobin in predicting future cardiovascular events of patients with advanced atherosclerosis. Circulation2003; 108:2323-8.
