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(Circulation. 2004;110:1940-1945.)
© 2004 American Heart Association, Inc.

Coronary Heart Disease

Growth Factors in the Collateral Circulation of Chronic Total Coronary Occlusions

Relation to Duration of Occlusion and Collateral Function

Gerald S. Werner, MD; Enrico Jandt, PhD; Andreas Krack, MD; Gero Schwarz, MD; Oliver Mutschke, MD; Friedhelm Kuethe, MD; Markus Ferrari, MD; Hans R. Figulla, MD

From the Clinic for Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany.

Reprint requests to Gerald S. Werner, MD PhD, Klinik für Innere Medizin I, Friedrich-Schiller-Universität, Erlanger Allee 101, D-07740 Jena, Germany. E-mail gerald.werner{at}med.uni-jena.de

Received May 6, 2004; revision received August 7, 2004; accepted August 12, 2004.

Background— Despite extensive animal experimental evidence, there are few data on the relation of growth factors and collateral function in humans.

Methods and Results— In 104 patients with a chronic total coronary occlusion (CTO; >2 weeks’ duration), collateral function was assessed invasively during recanalization by intracoronary Doppler and pressure recordings. A collateral resistance index, R_Coll, was calculated. Blood samples were drawn from the distal coronary bed supplied by the collaterals and from the aortic root to measure basic fibroblast growth factor (bFGF), monocytic chemotactic protein-1 (MCP-1), transforming growth factor-ß (TGF-ß), placenta growth factor (PlGF), and tumor necrosis factor- (TNF-). The bFGF concentration in the collateralized artery was higher than in the aortic root (34±20 versus 18±14 pg/mL; P<0.001). bFGF was highest in recent occlusions (2 to 12 weeks) with the highest R_Coll. Higher collateral concentrations were also observed for MCP-1, TGF-ß, and PlGF, but without a close relation to the duration of occlusion. TNF- was not increased in collaterals compared with the systemic circulation. MCP-1, PlGF, and TGF-ß were significantly increased in small collaterals with the highest shear stress. Diabetic patients had lower bFGF and higher MCP-1 levels than nondiabetics.

Conclusions— In CTOs, the continuous release of bFGF into collaterals showed a close relation to the duration of occlusion and collateral function, which underscores its therapeutic potential. Other factors influencing growth factor release appeared to be shear stress for MCP-1, TGF-ß, and PlGF and the presence of diabetes.

Key Words: collateral circulation • growth substances • angiogenesis • coronary disease

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