Aleksander Siniarski1, Stephen R Baker2, Cédric Duval3, Krzysztof P Malinowski4, Grzegorz Gajos1, Jadwiga Nessler1, Robert A S Ariëns5. 1. Department of Coronary Disease and Heart Failure, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland. 2. Leeds Thrombosis Collective, Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK; Department of Physics, Wake Forest University, Winston Salem, NC, USA. Electronic address: BakerSR@wfu.edu. 3. Leeds Thrombosis Collective, Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK. 4. 2nd Department of Cardiology, Jagiellonian University Medical College, Krakow, Poland. 5. Leeds Thrombosis Collective, Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK. Electronic address: R.A.S.Ariens@lees.ac.uk.
Abstract
INTRODUCTION: Coronary artery disease is associated with impaired clot structure. The aim of this study was to investigate acute phase myocardial infarction (AMI) and provide detailed quantitative analysis of clot ultrastructure. MATERIALS AND METHODS: Clot formation and breakdown, pore size, fiber density, fiber radius and protofibril packing were investigated in plasma clots from AMI patients. These data were compared to those from healthy controls. RESULTS: Analysis on clot formation using turbidity showed increased lag time, suggesting changes in protofibril packing and increased fiber size for AMI patients compared to healthy controls. Additionally, increased average rate of clotting and decreased time to maximum absorbance in AMI patients suggest that clots formed more quickly. Moreover, we observed increased time from max OD to max rate of lysis. Increased fibrinogen and decreased plasminogen in AMI patients were accounted for in represented significant differences. AMI samples showed increased time to 25% and 50% lysis, but no change in 75% lysis, representative of delayed lysis onset, but expediated lysis once initiated. These data suggest that AMI patients formed less porous clots made from more densely packed fibers with decreased numbers of protofibrils, which was confirmed using decreased permeation and increased fiber density, and decreased turbidimetry. CONCLUSIONS: AMI plasma formed clots that were denser, less permeable, and lysed more slowly than healthy controls. These findings were confirmed by detailed analysis of clot ultrastructure, fiber size, and protofibril packing. Dense clot structures that are resistant to lysis may contribute to a prothrombotic milieu in AMI.
INTRODUCTION:Coronary artery disease is associated with impaired clot structure. The aim of this study was to investigate acute phase myocardial infarction (AMI) and provide detailed quantitative analysis of clot ultrastructure. MATERIALS AND METHODS: Clot formation and breakdown, pore size, fiber density, fiber radius and protofibril packing were investigated in plasma clots from AMIpatients. These data were compared to those from healthy controls. RESULTS: Analysis on clot formation using turbidity showed increased lag time, suggesting changes in protofibril packing and increased fiber size for AMIpatients compared to healthy controls. Additionally, increased average rate of clotting and decreased time to maximum absorbance in AMIpatients suggest that clots formed more quickly. Moreover, we observed increased time from max OD to max rate of lysis. Increased fibrinogen and decreased plasminogen in AMIpatients were accounted for in represented significant differences. AMI samples showed increased time to 25% and 50% lysis, but no change in 75% lysis, representative of delayed lysis onset, but expediated lysis once initiated. These data suggest that AMIpatients formed less porous clots made from more densely packed fibers with decreased numbers of protofibrils, which was confirmed using decreased permeation and increased fiber density, and decreased turbidimetry. CONCLUSIONS:AMI plasma formed clots that were denser, less permeable, and lysed more slowly than healthy controls. These findings were confirmed by detailed analysis of clot ultrastructure, fiber size, and protofibril packing. Dense clot structures that are resistant to lysis may contribute to a prothrombotic milieu in AMI.
Authors: Ali Daraei; Marlien Pieters; Stephen R Baker; Zelda de Lange-Loots; Aleksander Siniarski; Rustem I Litvinov; Caroline S B Veen; Moniek P M de Maat; John W Weisel; Robert A S Ariëns; Martin Guthold Journal: Biomolecules Date: 2021-10-18