Abstract 18193: Distinct Effects of Unfractionated Heparin and Bivalirudin on Circulating Pro-Angiogenic Peptides
Unfractionated heparin (UFH) and bivalirudin (Bival) are commonly employed anticoagulants during percutaneous coronary intervention (PCI). Soluble fms-like tyrosine kinase 1 (sFLT1) is a circulating form of the Type 1 vascular endothelial growth factor (VEGF) receptor. sFLT1 levels are elevated in acute myocardial infarction and associated with thrombocytopenia and renal dysfunction. We explored whether anticoagulant therapy during PCI modulates circulating levels of sFLT1 and its ligands VEGF and placental growth factor (PlGF).
Methods & Results: We measured sFLT1, PlGF, and VEGF levels by enzyme linked immunosorbent assays (ELISA) in 16 patients undergoing elective PCI. Compared to baseline values, sFLT1 and PlGF levels increased by 2629±313% and 253±54%, respectively, within 30 minutes of UFH therapy (p<0.01 for both; n=8). VEGF levels decreased by 93.2±5% in patients treated with UFH (p<0.01 vs baseline). No change in sFLT1, PlGF, or VEGF levels were observed in any patients receiving Bival (n=8). To explore the direct effect of anticoagulation without patient heterogeneity, adult, male wild-type mice received venous injections of clinically dosed UFH or Bival. Compared to saline controls, sFLT1 and PlGF levels increased by >500% (p<0.01, for both) and VEGF levels increased by 221±101% (p<0.05) 30 minutes after UFH treatment. Neither Bival or dermatan sulfate (positive control for UFH) affected peptide levels. To study whether PlGF modulates sFLT1 or VEGF levels, PlGF knockout (−/−) mice were treated with UFH or Bival. Compared to controls, sFLT1 and VEGF levels increased by 1713±779% and 219±128% in PlGF−/− mice (p<0.01, for both) with undetectable PlGF levels after UFH. Bival had no effect on peptide levels. To study the cellular origin of peptides after anticoagulant therapy, human coronary endothelial cells were treated with UFH and demonstrated increased sFLT1 and PlGF levels (ANOVA p<0.01 for both) with reduced VEGF levels (ANOVA p<0.05). Bival had no effect on protein levels.
Conclusions: Circulating levels of sFLT1, PlGF, and VEGF are significantly altered by UFH, while Bival therapy has no effect. These findings may have implications for patients receiving anticoagulant therapy and clinical trials involving angiogenic peptides.
- © 2010 by American Heart Association, Inc.