P184	Collateral growth in patients with chronic total coronary occlusions: enhanced proliferative activity in the collateral circulation of diabetics.
1V.Tchaikovski, 2G.Werner, 2M.Fritzenwanger, 2E.Jandt, 1J.Waltenberger
1Department of Cardiology, Maastricht University Medical Center, and Cardiovascular Research Institute Maastricht, Maastricht, NL; 2Clinic for Internal Medicine I, Friedrich-Schiller-University Jena, Jena, DE.

Despite extensive preclinical evidence, there are few data demonstrating a functional role of growth factors (GF) in the development of collateral arteries in patients. It has been shown that patients with diabetes mellitus (DM) have a reduced number of collaterals and reduced collateral function. Recently, elevated levels of bFGF, PlGF and MCP-1 were shown in patients with chronic total coronary occlusions (CTOs). In the present study we have investigated the total proliferative activity (angiogenic potential) of serum from the collateral circulation (CC) and compared this with the proliferative activity in the systemic circulation (SC) in patients with CTOs. In 42 patients with CTOs blood was collected distal to the occlusion (CC) and from the aortic root (SC) immediately prior to revascularization. The mitogenic activity of different sera was assessed using human umbilical vein endothelial cells (HUVEC) in vitro and a 3H-thymidine incorporation-based proliferation assay. In patients without DM the ability to stimulate endothelial proliferation was significantly lower in CC compared to SC (p<0.02, n=23). Such a difference could not be observed in serum from diabetic patients where proliferative capacity of serum from CC was higher, reaching the level of serum from SC (n.s., n=16). In patients without identifiable previous myocardial infarction (MI), the proliferative activity of serum from CC was significantly lower than from SC (p<0.05, n=26), a situation similar to the one in non-diabetic patients. Likewise, in patients with normal regional myocardial function, the proliferative activity of serum from CC was significantly lower than from SC (p<0.02, n=22), while in patients with reduced regional myocardial function, no such a difference could be observed. In conclusion, the serum from CC from patients without DM has reduced proliferative activity on endothelial cells, i.e. reduced angiogenic potential. In patients with DM and in patients with a clear previous MI or with impaired regional myocardial function, this gradient is eliminated and the proliferative activity is enhanced in serum from CC. Our data are consistent with the hypothesis that the angiogenic potential is increased in patients with impaired collateral development. These data support a crucial role of GF in the development of collateral circulation.

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