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
Diabetologia
Published in: Diabetologia 7/2008

01-07-2008 | Article

Generalised reduction of putative endothelial progenitors and CXCR4-positive peripheral blood cells in type 2 diabetes

Authors: C. G. Egan, R. Lavery, F. Caporali, C. Fondelli, F. Laghi-Pasini, F. Dotta, V. Sorrentino

Published in: Diabetologia | Issue 7/2008

Login to get access

Abstract

Aims/hypothesis

In patients with type 2 diabetes, reduced levels of circulating endothelial progenitor cells have been reported and these have been correlated with disease severity. In this study, we examined a panel of markers widely used to identify progenitor and/or stem cells, and determined their association with disease severity in diabetic patients. Since expression of chemokine (C-X-C motif) receptor 4 (CXCR4) has been associated with mobilisation and recruitment of progenitor cells, CXCR4 expression was also analysed.

Methods

Peripheral blood mononuclear cells (PBMCs) from 98 patients with type 2 diabetes and 39 control individuals were analysed by flow cytometry for surface marker expression.

Results

Cells expressing different combinations of progenitor and/or stem cell markers were severely reduced in PBMCs of diabetic patients compared with those of control participants. Moreover, a number of these putative progenitor cell populations were negatively associated with disease severity. Reduced expression of CXCR4 and CD34/CXCR4-positive cells was also observed in diabetic patients. PBMCs expressing CXCR4 positively correlated with levels of progenitor cells in control participants but not in diabetic patients. Levels of putative progenitor and CXCR4-positive cells were further decreased in patients with diabetic complications, including cardiovascular and microvascular diseases.

Conclusions/interpretation

A generalised decrease in a range of progenitor cell populations was observed in type 2 diabetic patients. This reduction was also negatively associated with disease severity.
Appendix
Available only for authorised users
Literature
1.
Waltenberger J (2001) Impaired collateral vessel development in diabetes: potential cellular mechanisms and therapeutic implications. Cardiovasc Res 16:554–560CrossRef
2.
St Clair L, Ballantyne CM (2007) Biological surrogates for enhancing cardiovascular risk prediction in type 2 diabetes mellitus. Am J Cardiol 99:80–88CrossRef
3.
Stumvoll M, Goldstein BJ, van Haeften TW (2005) Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365:1333–1346PubMedCrossRef
4.
Landmesser U, Drexler H (2005) The clinical significance of endothelial dysfunction. Curr Opin Cardiol 20:547–551PubMedCrossRef
5.
Deanfield JE, Halcox JP, Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115:1285–1295PubMed
6.
7.
Takahashi T, Kalka C, Masuda H et al (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434–438PubMedCrossRef
8.
Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967PubMedCrossRef
9.
Hristov M, Wolfgang W, Weber PC (2003) Endothelial progenitor cells—mobilization differentiation and homing. Arterioscler Thromb Vasc Biol 23:1185–1189PubMedCrossRef
10.
Ingram DA, Caplice NM, Yoder MC (2005) Unresolved questions, changing definitions, and novel paradigms for defining endothelial progenitor cells. Blood 106:1525–1531PubMedCrossRef
11.
Case J, Mead LE, Bessler WK et al (2007) Human CD34 + AC133 + VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol 35:1109–1118PubMedCrossRef
12.
Hur J, Yoon CH, Kim HS et al (2004) Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 24:288–293PubMedCrossRef
13.
Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353PubMedCrossRef
14.
Vasa M, Fichtlscherer S, Aicher A et al (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89:E1–E7PubMedCrossRef
15.
Shantsila E, Watson T, Lip GY (2007) Endothelial progenitor cells in cardiovascular disorders. J Am Coll Cardiol 49:741–752PubMedCrossRef
16.
Grisar J, Aletaha D, Steiner CW et al (2005) Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 111:204–211PubMedCrossRef
17.
Fadini GP, Schiavon M, Cantini M et al (2006) Circulating progenitor cells are reduced in patients with severe lung disease. Stem Cells 24:1806–1813PubMedCrossRef
18.
Fadini GP, Miorin M, Facco M et al (2005) Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 45:1449–1457PubMedCrossRef
19.
Tepper OMGR, Capla JM, Kalka C et al (2002) Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation adhesion and incorporation into vascular structures. Circulation 106:2781–2786PubMedCrossRef
20.
Loomans CJ, de Koning EJ, Staal FJ et al (2004) Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 53:195–199PubMedCrossRef
21.
Massa M, Rosti V, Ferrario M et al (2005) Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infaction. Blood 105:199–205PubMedCrossRef
22.
Isner JM, Asahara T (1999) Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest 103:1231–1236PubMedCrossRef
23.
Kucia M, Ratajczak J, Ratajczak MZ (2005) Bone marrow as a source of circulating CXCR4 + tissue-committed stem cells. Biol Cell 97:133–146PubMedCrossRef
24.
Ceradini DJ, Gurtner GC (2005) Homing to hypoxia: HIF-1 as a mediator of progenitor cell recruitment to injured tissue. Trends Cardiovasc Med 15:57–63PubMedCrossRef
25.
Ruiz de Almodovar C, Luttun A, Carmeliet P (2006) An SDF-1 trap for myeloid cells stimulates angiogenesis. Cell 124:18–21PubMedCrossRef
26.
Yamaguchi J, Kusano KF, Masuo O et al (2003) Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 107:1322–1328PubMedCrossRef
27.
Walter DH, Haendeler J, Reinhold J et al (2005) Impaired CXCR4 signaling contributes to the reduced neovascularisation capacity of endothelial progenitor cells from patients with coronary artery disease. Circ Res 97:1142–1151PubMedCrossRef
28.
American Diabetes Association (2007) Standards of medical care in diabetes—2007. Diabetes Care 30(Suppl 1):S4–S41CrossRef
29.
Grundy SM, Cleeman JI, Merz CN et al (2004) Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110:227–239PubMedCrossRef
30.
Miller DD, Shaw LJ (2006) Foreword: cardiovascular disease: diagnostic, prognostic, and measurement paradigms for reducing patient risk. J Cardiovasc Nurs 21(6 Suppl 1):S1PubMed
31.
Devendra D, Farmer K, Bruce G, Hughes P, Vivian G, Millward BA (2001) Diagnosing osteomyelitis in patients with diabetic neuropathic osteoarthropathy. Diabetes Care 24:2154–2155PubMedCrossRef
32.
Cypress M, Tomky D (2006) Microvascular complications of diabetes. Nurs Clin North Am 41:719–736 ixPubMedCrossRef
33.
Molitch ME, DeFronzo RA, Franz MJ et al (2004) American Diabetes Association. Nephropathy in diabetes. Diabetes Care Suppl 1:S79–S83
34.
Rogler G, Hausmann M, Vogl D et al (1998) Isolation and phenotypic characterization of colonic macrophages. Clin Exp Immunol 112:205–215PubMedCrossRef
35.
Wang XX, Zhang FR, Shang YP et al (2007) Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial. J Am Coll Cardiol 49:1566–1571PubMedCrossRef
36.
Fadini GP, Sartore S, Agostini C, Avogaro A (2007) Significance of endothelial progenitor cells in subjects with diabetes. Diabetes Care 30:1305–1313PubMedCrossRef
37.
Kusuyama T, Omura T, Nishiya D et al (2006) Effects of treatment for diabetes mellitus on circulating vascular progenitor cells. J Pharmacol Sci 102:96–102PubMedCrossRef
38.
Naruse K, Hamada Y, Nakashima E et al (2005) Therapeutic neovascularization using cord blood-derived endothelial progenitor cells for diabetic neuropathy. Diabetes 54:1823–1828PubMedCrossRef
39.
Fadini GP, Sartore S, Baesso I et al (2006) Endothelial progenitor cells and the diabetic paradox. Diabetes Care 29:714–716PubMedCrossRef
40.
Lee IG, Chae SL, Kim JC (2006) Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy. Eye 20:546–552PubMedCrossRef
41.
Butler JM, Guthrie SM, Koc M et al (2005) SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest 115:86–93PubMed
42.
Damas JK, Waehre T, Yndestad A et al (2002) Stromal cell-derived factor-1alpha in unstable angina: potential antiinflammatory and matrix-stabilizing effects. Circulation 106:36–42PubMedCrossRef
43.
Honold J, Lehmann R, Heeschen C et al (2006) Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arterioscler Thromb Vasc Biol 26:2238–2243PubMedCrossRef
44.
Segal MS, Shah R, Afzal A et al (2006) Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. Diabetes 55:102–109PubMedCrossRef
45.
Humpert PM, Neuwirth R, Battista MJ et al (2005) SDF-1 genotype influences insulin-dependent mobilization of adult progenitor cells in type 2 diabetes. Diabetes Care 28:934–936PubMedCrossRef
46.
Fadini GP, Sartore S, Schiavon M et al (2006) Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia-reperfusion injury in rats. Diabetologia 49:3075–3084PubMedCrossRef
47.
Gallagher KA, Liu ZJ, Xiao M et al (2007) Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1. J Clin Invest 117:1249–1259PubMedCrossRef
Metadata
Title
Generalised reduction of putative endothelial progenitors and CXCR4-positive peripheral blood cells in type 2 diabetes
Authors
C. G. Egan
R. Lavery
F. Caporali
C. Fondelli
F. Laghi-Pasini
F. Dotta
V. Sorrentino
Publication date
01-07-2008
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-0939-6

Other articles of this Issue 7/2008

Diabetologia 7/2008 Go to the issue

Letter

Insulin may have a role to play in protecting beta cells from deterioration in diabetes

Article

Pancreatic islet isolation variables in non-human primates (rhesus macaques)

Commentary

IL-6 and metabolism—new evidence and new questions

Article

Stepwise screening for diabetes identifies people with high but modifiable coronary heart disease risk. The ADDITION study

Short Communication

Post-challenge blood glucose concentration and stroke mortality rates in non-diabetic men in London: 38-year follow-up of the original Whitehall prospective cohort study

Article

Exercise restores endothelial function independently of weight loss or hyperglycaemic status in db/db mice
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

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits