Key result
Exposure to 300 μM SNAP for 1 hour significantly reduced thrombin-induced fibrin formation to 50% of baseline compared to 95% with NAP, likely via fibrinogen conformational changes.
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NO donors such as SNAP induce fibrinogen conformational changes, which may provide a mechanism for improving thromboresistance in extracorporeal circulation.
study evaluated the released NO effects on the thrombin-mediated fibrin formation and fibrinogen structure. Thrombin-induced fibrin formation at 300 μM SNAP (50 + 11% of baseline) was significantly reduced compared to SNAP's parent, N-acetyl-penicillamine (NAP) (95 + 13%) after 1 h of RSNO exposure. GSNO, its parent, glutathione (GSH) and 1000 ppm NO gas did not attenuate the thrombin-mediated fibrin formation. SNAP, NAP and SNP exposure for 1 h, however, did not decrease thrombin activity by directly inhibiting thrombin itself. Changes in fibrinogen conformation as measured by intrinsic tryptophan fluorescence significantly decreased in the 300 μM SNAP (38057 + 1196 mean fluorescence intensity (MFI) and SNP (368617 + 541 MFI) groups versus the NAP control (47937 + 1196 MFI). However, infused 1000 ppm NO gas had no direct effect on the ITF after 1 h incubation at 37°C. High performance liquid chromatography (HPLC) showed that fibrinogen degradation by 0.03 U/ml thrombin was concentration-dependently reduced after 1 h with SNAP but not with NAP or SNP. Western blotting showed RSNOs, SNAP, NAP and the non-RSNO, SNP-incubated fibrinogen solutions showed that the percent level of the Aγ dimer to total Aγ dimer + γ monomer was significantly reduced in the case of the SNAP group when compared to SNP group. These results suggest that NO donors such as SNAP and SNP induce fibrinogen conformational changes by potentially nitrosating fibrinogen tyrosine residues. These NO-mediated fibrinogen changes induced via NO donors may provide another mechanism of NO for improving thromboresistance in ECC.
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Major et al. (2018) studied this question. S-nitroso-N-acetylpenicillamine (SNAP) vs. N-acetyl-penicillamine (NAP) was evaluated on Thrombin-induced fibrin formation (% of baseline). Exposure to 300 μM SNAP for 1 hour significantly reduced thrombin-induced fibrin formation to 50% of baseline compared to 95% with NAP, likely via fibrinogen conformational changes.
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