Advertisement

Molecular Medicine

, Volume 14, Issue 5–6, pp 235–237 | Cite as

The IGF-1 Receptor as a Therapeutic Target to Improve Endothelial Progenitor Cell Function

  • Felix Fleissner
  • Thomas Thum
Commentary
Bone marrow-derived circulating endothelial progenitor cells (EPC) participate in angiogenesis and vascular homeostasis by incorporating into the endothelium of damaged vessels and, perhaps more importantly, exhibiting potent angiogenic paracrine effects ( 1). EPC are embedded in the microenvironment of bone marrow stromal and endothelial cells and translocate to the circulation upon NO-mediated signaling ( 2). Additional mobilizing pathways include extracellular signal-regulated kinases (ERK)/matrix metalloproteinase-9 (MMP-9)-mediated release of soluble c-Kit ligand ( 3). EPC participate in postnatal growth of new blood vessels and/or are home to sites of endothelial damage, maintaining endothelial integrity and function. Circulating EPC numbers are tightly correlated to endothelial function and serve as an independent predictor for cardiovascular diseases ( 4). Functionalproperties of EPC may be of equal or greater importance than quantitative alterations. A variety of functional...

References

  1. 1.
    Bauersachs J, Thum T. (2007) Endothelial progenitor cell dysfunction: mechanisms and therapeutic approaches. Eur. J. Clin. Invest. 37:603–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Aicher A et al. (2003) Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat. Med. 9:1370–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Heissig B et al. (2003) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 109:625–637.CrossRefGoogle Scholar
  4. 4.
    Werner N et al. (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N. Engl. J. Med. 353:999–1007.CrossRefPubMedGoogle Scholar
  5. 5.
    Heeschen C, Hamm CW, Mitrovic V, Lantelme NH, White HD. (2005) Platelet receptor inhibition in ischemic syndrome management (PRISM) investigators. N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes. Circulation. 110:3206–12.CrossRefGoogle Scholar
  6. 6.
    Thum T et al. (2007) Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes. Diabetes. 56:666–74.CrossRefPubMedGoogle Scholar
  7. 7.
    Thum T et al. (2007) Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulinlike growth-factor-1. Circ. Res. 100:434–43.CrossRefPubMedGoogle Scholar
  8. 8.
    Thum T et al. (2007) Growth hormone treatment improves markers of systemic nitric oxide bioavailability via insulin-like growth factor-I. J. Clin. Endocrinol. Metab. 92:4172–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Humpert PM et al. (2008) Insulin stimulates the clonogenic potential of angiogenic endothelial progenitor cells by IGF-1 receptor dependent signaling. Mol. Med. 14:301–308.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Böger RH et al. (1996) Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J. Clin. Invest. 98:2706–13.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Franklin VL, Khan F, Kennedy G, Belch JJ, Greene SA. (2008) Intensive insulin therapy improves endothelial function and microvascular reactivity in young people with type 1 diabetes. Diabetologia. 51:353–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Nathan Cleary PA et al. (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med. 353:2643–53.CrossRefPubMedGoogle Scholar
  13. 13.
    Kurtzhals P et al. (2000) Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes. 49:999–1005.CrossRefPubMedGoogle Scholar
  14. 14.
    Thum T et al. (2005) Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. J. Am. Coll. Cardiol. 46:1693–701.CrossRefPubMedGoogle Scholar
  15. 15.
    Ellger B et al. (2008) Glycemic control modulates arginine- and ADMA-levels during critical illness by preserving DDAH-activity. Endocrinology. 2008, Feb 21 [Epub ahead of print].Google Scholar
  16. 16.
    Bogdanski P et al. (2007) Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus. Int. J. Clin. Pharmacol. Ther. 45:563–7.CrossRefPubMedGoogle Scholar

Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  1. 1.Medizinische Klinik I (Kardiologie), Internal Medicine, Department of CardiologyJulius-Maximilians UniversitätWürzburgGermany

Personalised recommendations