Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Endocrine Disorders
Published in: BMC Endocrine Disorders 1/2010

Open Access 01-12-2010 | Research article

Comparison of endothelial progenitor cell function in type 2 diabetes with good and poor glycemic control

Authors: Worachat Churdchomjan, Pakpoom Kheolamai, Sirikul Manochantr, Pirath Tapanadechopone, Chairat Tantrawatpan, Yaowalak U-pratya, Surapol Issaragrisil

Published in: BMC Endocrine Disorders | Issue 1/2010

Login to get access

Abstract

Background

Endothelial progenitor cells (EPCs) play an important role in vascular repair and a decrease in the number of EPCs is observed in type 2 diabetes. However, there is no report on the change of EPCs after glycemic control. This study therefore aimed to investigate the EPC number and function in patients with good and poor glycemic control.

Methods

The number of EPCs was studied using flow cytometry by co-expression of CD34 and VEGFR2. The EPCs were cultured and characterized by the expression of UEA-I, CD34, VEGFR2, vWF and Dil-Ac-LDL engulfment, as well as the ability to form capillary-like structures. An in vitro study on the effect of hyperglycemia on the proliferation and viability of the cultured EPCs was also performed.

Results

The number of EPCs in type 2 diabetes was significantly decreased compared with healthy controls and there was an inverse correlation between the EPC numbers and plasma glucose, as well as HbA1C. The number and function of EPCs in patients with good glycemic control were recovered compared with those with poor glycemic control. When glucose was supplemented in the culture in vitro, there was a negative effect on the proliferation and viability of EPCs, in a dose-dependent manner, whereas the enhancement of apoptosis was observed.

Conclusion

There was EPC dysfunction in type 2 diabetes which might be improved by strict glycemic control. However, the circulating EPC number and proliferative function in patients with good glycemic control did not reach the level in healthy controls.
Appendix
Available only for authorised users
Literature
1.
Hristov M, Zernecke A, Liehn EA, Weber C: Regulation of endothelial progenitor cell homing after arterial injury. ThrombHaemost. 2007, 98 (2): 274-7.
2.
Miller-Kasprzak E, Jagodzinski PP: Endothelial progenitor cells as a new agent contributing to vascular repair. Arch Immunol Ther Exp(Warsz). 2007, 55 (4): 247-59. 10.1007/s00005-007-0027-5.CrossRef
3.
Ballard VL, Edelberg JM: Targets for regulating angiogenesis in the aging endothelium. Expert Opin Ther Targets. 2007, 11 (11): 1385-99. 10.1517/14728222.11.11.1385.CrossRefPubMed
4.
Werner N, Nickenig G: Clinical and therapeutical implications of EPC biology in atherosclerosis. J Cell Mol Med. 2006, 10 (2): 318-32. 10.1111/j.1582-4934.2006.tb00402.x.CrossRefPubMed
5.
Asahara T, Murohara T, Sullivan MA, Silver M, Zee van der R, Li T: Isolation of putative progenitor endothelialcells for angiogenesis. Science. 1997, 275: 964-7. 10.1126/science.275.5302.964.CrossRefPubMed
6.
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A: Circulating endothelial progenitor cells andcardiovascular outcomes. N Engl J Med. 2005, 353 (10): 999-1007. 10.1056/NEJMoa043814.CrossRefPubMed
7.
Fadini GP, Sartore S, Schiavon M, Albiero M, Baesso I, Cabrelle A: Diabetes impairs progenitor cell mobilization after hindlimb ischaemia-reperfusion injury in rats. Diabetologia. 2006, 49 (12): 3075-84. 10.1007/s00125-006-0401-6.CrossRefPubMed
8.
Mukai N, Akahori T, Komaki M, Li Q, Kanayasu-Toyoda T, Ishii-Watabe A: A comparison of the tube forming potentials of early and late endothelial progenitor cells. Exp Cell Res. 2008, 314 (3): 430-40. 10.1016/j.yexcr.2007.11.016.CrossRefPubMed
9.
Fadini GP, Baesso I, Albiero M, Sartore S, Agostini C, Avogaro A: Technical notes on endothelial progenitor cells: ways to escape from the knowledge plateau. Atherosclerosis. 2008, 197 (2): 496-503. 10.1016/j.atherosclerosis.2007.12.039.CrossRefPubMed
10.
Urbich C, Dimmeler S: Endothelial progenitor cells: characterization and role in vascular biology. Circ Res. 2004, 95 (4): 343-53. 10.1161/01.RES.0000137877.89448.78.CrossRefPubMed
11.
Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR: Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002, 106 (22): 2781-6. 10.1161/01.CIR.0000039526.42991.93.CrossRefPubMed
12.
Loomans CJ, De Koning EJ, Staal FJ, Rabelink TJ, Zonneveld AJ: Endothelial progenitor cell dysfunction in type 1 diabetes: another consequence of oxidative stress?. Antioxid Redox Signal. 2005, 7 (11-12): 1468-75. 10.1089/ars.2005.7.1468.CrossRefPubMed
13.
Ding H, Triggle CR: Endothelial cell dysfunction and the vascular complications associated with type II diabetes: assessing the health of the endothelium. Vasc Health Risk Manag. 2005, 1 (1): 55-71. 10.2147/vhrm.1.1.55.58939.CrossRefPubMedPubMedCentral
14.
Snyder RJ: Controversies regarding vascular disease in the patient with diabetes: a review of the literature. Ostomy Wound Manage. 2007, 53 (11): 40-8.PubMed
15.
American Diabetes Association (ADA): Clinical practice recommendation. Diabetes Care. 2002, 25 (Suppl 1): S1-147.
16.
Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M: Number and function of endothelial progenitorcells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006, 26 (9): 2140-6. 10.1161/01.ATV.0000237750.44469.88.CrossRefPubMed
17.
Mosmann T: Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxicity assays. JImmunol Methods. 1983, 65: 55-63. 10.1016/0022-1759(83)90303-4.CrossRef
18.
Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C: A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labeled annexin V. J Immunol Methods. 1995, 184: 39-51. 10.1016/0022-1759(95)00072-I.CrossRefPubMed
19.
Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H: Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001, 89 (1): E1-7. 10.1161/hh1301.093953.CrossRefPubMed
20.
Hill JM, Zalos G, Halcox JPJ, Schenke WH, Waclawiw MA, Quyyumi AA: Circulating endothelial pregenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003, 348: 593-600. 10.1056/NEJMoa022287.CrossRefPubMed
21.
Loomans CJM, de Koning EJP, Staal FJT, Rookmaaker MB, Verseyden C, de Boer HC: Endothelial progenitor cell dysfunction - A novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004, 53 (1): 195-9. 10.2337/diabetes.53.1.195.CrossRefPubMed
22.
Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F: Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type II diabetes mellitus. J Am CollCardiol. 2005, 45: 1149-57.CrossRef
23.
Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M: Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006, 26 (9): 2140-6. 10.1161/01.ATV.0000237750.44469.88.CrossRefPubMed
24.
Fadini GP, Pucci L, Vanacore R, Baesso I, Penno G, Balbarini A: Glucose tolerance is negatively associated with circulating progenitor cell levels. Diabetologia. 2007, 50 (10): 2156-63. 10.1007/s00125-007-0732-y.CrossRefPubMed
25.
Hill JM, Zalos G, Halcox JPJ, Schenke WH, Waclawiw MA, Quyyumi AA: Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003, 348 (7): 593-600. 10.1056/NEJMoa022287.CrossRefPubMed
26.
Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U: Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events - Proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005, 111 (22): 2981-7. 10.1161/CIRCULATIONAHA.104.504340.CrossRefPubMed
27.
Rosenzweig A: Circulating endothelial progenitors-cellsas biomarkers. N Engl J Med. 2005, 353 (10): 1055-7. 10.1056/NEJMe058134.CrossRefPubMed
28.
Fadini GP, Agostini C, Sartore S, Avogaro A: Endothelial progenitor cells in the natural history of atherosclerosis. Atherosclerosis. 2007, 194 (1): 46-54. 10.1016/j.atherosclerosis.2007.03.046.CrossRefPubMed
29.
Gallagher KA, Liu ZJ, Xiao M, Chen H, Goldstein LJ, Buerk DG: Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest. 2007, 117 (5): 1249-59. 10.1172/JCI29710.CrossRefPubMedPubMedCentral
30.
Kuki S, Imanishi T, Kobayashi K, Matsuo Y, Obana M, Akasaka T: Hyperglycemia accelerated endothelial progenitor cell senescence via the activation of p38 mitogen-activated protein kinase. Circ J. 2006, 70 (8): 1076-81. 10.1253/circj.70.1076.CrossRefPubMed
31.
Catrina SB, Okamoto K, Pereira T, Brismar K, Poellinger L: Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability andfunction. Diabetes. 2004, 53 (12): 3226-32. 10.2337/diabetes.53.12.3226.CrossRefPubMed
32.
Seeger FH, Haendeler J, Walter DH, Rochwalsky U, Reinhold J, Urbich C: p38 mitogen-activated protein kinase downregulates endothelial progenitor cells. Circulation. 2005, 111 (9): 1184-91. 10.1161/01.CIR.0000157156.85397.A1.CrossRefPubMed
33.
Marchetti V, Menghini R, Rizza S, Vivanti A, Feccia T, Lauro D: Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling. Diabetes. 2006, 55 (8): 2231-7. 10.2337/db06-0369.CrossRefPubMed
34.
Krankel N, Adams V, Linke A, Gielen S, Erbs S, Lenk K: Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arterioscler Thromb VascBiol. 2005, 25 (4): 698-703. 10.1161/01.ATV.0000156401.04325.8f.CrossRef
35.
Minami R, Muta K, Umemura T, Motomura S, Abe Y, Nishimura J: p16 (INK4a) induces differentiation and apoptosis in erythroid lineage cells. Exp Hematol. 2003, 31: 355-62. 10.1016/S0301-472X(03)00040-7.CrossRefPubMed
36.
Shukla S, Gupta S: Molecular mechanisms for apigenin-induced cell-cycle arrest and apoptosis of hormone refractory human prostate carcinoma DU145 cells. Mol Carcinog. 2004, 39: 114-26. 10.1002/mc.10168.CrossRefPubMed
37.
Seeger FH, Chen L, Spyridopoulos I, Altschmied J, Aicher A, Haendeler J: Downregulation of ETS rescues diabetes-induced reduction of endothelial progenitor cells. PLoS ONE. 2009, 4 (2): e4529-10.1371/journal.pone.0004529.CrossRefPubMedPubMedCentral
38.
Callaghan MJ, Ceradini DJ, Gurtner GC: Hyperglycemia-induced reactive oxygen species and impaired endothelial progenitor cell function. Antioxid Redox Signal. 2005, 7 (11-12): 1476-82. 10.1089/ars.2005.7.1476.CrossRefPubMed
39.
Fujii H, Li SH, Szmitko PE, Fedak PW, Verma S: C-reactiveprotein alters antioxidant defenses and promotes apoptosis in endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2006, 26 (11): 2476-82. 10.1161/01.ATV.0000242794.65541.02.CrossRefPubMed
40.
Rolo A, Palmeira C: Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol. 2006, 212: 167-78. 10.1016/j.taap.2006.01.003.CrossRefPubMed
41.
He T, Peterson TE, Holmuhamedov EL, Terzic A, Caplice NM, Oberley LW: Human endothelial progenitor cells tolerate oxidative stress due to intrinsically high expression of manganese superoxide dismutase. Arterioscler Thromb Vasc Biol. 2004, 24 (11): 2021-7. 10.1161/01.ATV.0000142810.27849.8f.CrossRefPubMed
42.
Chen YH, Lin SJ, Lin FY, Wu TC, Tsao CR, Huang PH: High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes. 2007, 56 (6): 1559-68. 10.2337/db06-1103.CrossRefPubMed
43.
Kim I, Kim HG, So JN, Kim JH, Kwak HJ, Koh GY: Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3'-Kinase/Akt signal transduction pathway. Circ Res. 2000, 86 (1): 24-9.CrossRefPubMed
44.
Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K: Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 1999, 399 (6736): 597-601. 10.1038/21218.CrossRefPubMedPubMedCentral
45.
Ho FM, Lin WW, Chen BC, Chao CM, Yang CR, Lin LY: High glucose-induced apoptosis in human vascular endothelial cells is mediated through NF-kappaB and c-Jun NH2-terminal kinase pathway and prevented by PI3K/Akt/eNOS pathway. Cell Signal. 2006, 18 (3): 391-9. 10.1016/j.cellsig.2005.05.009.CrossRefPubMed
46.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA: 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008, 359 (15): 1577-89. 10.1056/NEJMoa0806470.CrossRefPubMed
Metadata
Title
Comparison of endothelial progenitor cell function in type 2 diabetes with good and poor glycemic control
Authors
Worachat Churdchomjan
Pakpoom Kheolamai
Sirikul Manochantr
Pirath Tapanadechopone
Chairat Tantrawatpan
Yaowalak U-pratya
Surapol Issaragrisil
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2010
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/1472-6823-10-5

Other articles of this Issue 1/2010

BMC Endocrine Disorders 1/2010 Go to the issue

Research article

Hypothyroidism among military infants born in countries of varied iodine nutrition status

Research article

The transcription factor 7-like 2 (TCF7L2) polymorphism may be associated with focal arteriolar narrowing in Caucasians with hypertension or without diabetes: the ARIC Study

Case report

Symptomatic hypopituitarism revealing primary suprasellar lymphoma

Research article

Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes

Research article

Early limited nitrosamine exposures exacerbate high fat diet-mediated type 2 diabetes and neurodegeneration

Research article

Associations of age with serum insulin, proinsulin and the proinsulin-to-insulin ratio: a cross-sectional study
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits