Abstract 12146: Thymidine Phosphorylase Determines Improvement in Endothelial Function Following Cardiac Rehabilitation
Cardiac rehabilitation is thought to reduce morbidity and mortality in ischaemic heart disease (IHD) via improved endothelial function. Thymidine Phosphorylase (TP) is expressed by peripheral blood mononuclear cells (PBMNC) and influences the angiogenic activity of HUVEC. We hypothesised that PBMNC derived TP determines improved endothelial function in IHD patients following cardiac rehabilitation. Forty consecutive male IHD patients (58.6 ± 10.5 years) underwent a standard six-week exercise cardiac rehabilitation programme. Endothelial function was assessed by flow-mediated dilatation of the brachial artery. Following cardiac rehabilitation, FMD increased in 13 patients (Responders; 2.69 ± 0.29%; p<0.0001) whilst no increase was seen in the remaining 27 patients (Non-Responders; -0.37 ± 1.12%; p=0.15). Serum TP levels, assessed by Western Blot and ELISA, increased significantly in Responders but were unchanged in Non-Responders (20.7 ± 6ng/ml versus 3.8 ± 5ng/ml; p=0.04). Conditioned media of PBMNC cultured from Responder patients contained high TP levels, whereas it was undetectable in that from Non-Responders. The role of TP in the angiogenic behaviour of HUVEC (wound scratch and tube formation assays) was confirmed by the use of 5-Bromo-6-Amino-Uracil (5Br), a specific TP inhibitor, resulting in complete abrogation of HUVEC angiogenic activity; an effect reproduced by incubating HUVEC in Non-Responder PBMNC-conditioned media. HUVEC showed increased angiogenic activity when exposed to conditioned media from Responders. Moreover, the angiogenic activity of HUVEC exposed to Non-Responder conditioned media was rescued when supplemented with that from Responders. In conclusion, TP plays a critical role in the angiogenic behaviour of HUVEC, and its expression in IHD patients determines improved FMD following cardiac rehabilitation, providing a mechanism for modulating endothelial function via the manipulation of TP expression.
- © 2011 by American Heart Association, Inc.