Bivalirudin Inhibits Periprocedural Platelet Function and Tissue Factor Expression of Human Smooth Muscle Cells

Abstract

SUMMARYAim: A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. In this study, we examined the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration. Further, the effect of bivalirudin on induced tissue factor (TF) expression in smooth muscle cells (SMC) was determined. Methods: Patients with CAD (n = 58) and double antithrombotic medication were treated intraprocedural with UFH (n = 30) or bivalirudin (n = 28). Platelet activation markers were flow cytometrically measured before and after stenting. The expression of TF in SMC was determined by real-time PCR and Western blotting. The thrombogenicity of platelet-derived microparticles and SMC was assessed via a TF activity assay. Results: Bivalirudin significantly diminished the agonist-induced platelet reactivity post-PCI. Compared to UFH treatment, the adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP)-induced thrombospondin expression post-PCI was reduced when bivalirudin was administrated during intervention. In contrast to UFH, bivalirudin reduced the P-selectin expression of unstimulated and ADP-induced platelets post-PCI. Moreover, bivalirudin inhibited the thrombin-, but not FVIIa-or FVIIa/FX-induced TF expression and pro-coagulant TF activity of SMC. Moreover, bivalirudin reduced the TF activity of platelet-derived microparticles postinduction with TRAP or ADP. Conclusions: Bivalirudin is better than UFH in reducing periprocedural platelet activation. Moreover, thrombin-induced TF expression is inhibited by bivalirudin. Thus, bivalirudin seems to be a better anticoagulant during PCI than UFH.

Bivalirudin Inhibits Thrombin-Mediated Tissue Factor Expression in Human Endothelial Cells

“…Previous report has indicated that Bivalirudin inhibits TF expression in smooth muscle cells that constitutively express this glycoprotein [8]. In the present manuscript, we demonstrate that Bivalirudin is able to inhibit thrombin-induced TF expression in a cell population of the vessel wall never investigated before in this setting such as endothelial cells.…”

Bivalirudin versus unfractionated heparin for residual thrombus burden: A frequency‐domain optical coherence tomography study

“…In our study, the use of bivalirudin was associated with a significantly lower proportion of platelet‐rich (white) thrombus. Previous evidence suggests that ADP‐induced platelet activation is significantly lower with bivalirudin than UFH, and that bivalirudin reduces thrombin‐induced tissue factor form expression and activity . Moreover, bivalirudin does not induce the ultra‐structural changes associated with platelet activation, such as pseudopodia extrusions and increased P‐selectin expression, typically observed with UFH .…”

The role of tissue factor isoforms in cancer biology

“…18,25 Post-transcriptional expression control regulate a variety of biologic functions, such as tumor cell invasion, thrombogenicity, metastasis, chemotaxis, growth and angiogenesis in cancer as well as in other pathophysiologic-relevant settings, such as the cardiovascular system. [15][16][17][18]26,27 Two major mechanisms modulate post-transcriptional expression: alternative splicing and micro (mi)RNAs. 16 The biogenesis of miRNAs as well as the functionality of miRNAs and alternative splicing processes were reviewed in detail elsewhere.…”