Thorac Cardiovasc Surg 2005; 53 - P_18
DOI: 10.1055/s-2005-922380

Modulation of proliferation and function of progenitor cells by diabetes and age associated advanced glycation endproducts (AGEs)

RJ Scheubel 1, I Friedrich 1, J Börgermann 1, RE Silber 1, A Simm 1
  • 1Martin-Luther-University Halle-Wittenberg, Department of cardiothoracic surgery, Halle (Saale), Germany

Despite ageing and diabetes are major risk factors for adverse outcome, the number of older patients with concomitant diabetes undergoing cardiac surgery increased during last years. Additionally, diabetes and ageing induce reduction and dysfunction of progenitor cells, which are discussed to contribute to reparative neovascularization. Advanced glycation endproducts (AGEs) accumulate in both diabetes and ageing. Therefore we investigated the influence of AGEs on behavior of progenitor cells. During co-culture of CD34 progenitor cells with HUVECs in an angiogenesis model, we found a dose dependent reduction of sprout length formation and of the incorporation of progenitor cells into developing branches with increasing AGEs doses (2, 20, 200µg/ml). 2 and 20µg/ml of AGEs promoted CD34 proliferation by 35.6 res. 73.3% (p=0.05) whereas 200µg/ml AGEs reduced cell number by 34.3% (p=0.004). This may be influenced by an increase of apoptosis by 52.9% under 200µg/ml AGEs (p=0.004) while 2 and 20µg/ml AGEs reduced apoptosis by 11.2 res. 1.9% (n.s.) whereas cell cycle was not affected by AGEs. To investigate putative cellular signalling the expression of five known receptors for AGEs (AGE-R1-R3, RAGE, CD36) were analyzed and could be verified in CD34 cells using PCR. The stimulation of p38MAPK and p42/44MAPK were shown under AGEs using Western-blotting and activation-specific antibodies. In summary, AGEs seem to play a critical role in the biology of progenitor cells and could be a pathophysiological link between diabetes and ageing.