PB0848 - Platelets modulate cardiac remodeling via the collagen receptor GPVI after acute myocardial infarction

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Friedrich WB Reusswig, PhD

Postdoctoral Research Fellow
Center for Thrombosis and Hemostasis
Mainz, Rheinland-Pfalz, Germany

Co-Author(s)

MD

Matthias Dille

Postdoctoral Research Fellow
Department of Vascular- and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany
Duessledorf.de, Nordrhein-Westfalen, Germany
EK

Evelyn Krueger

Postdoctoral Research Fellow
Department of Vascular- and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany
Duesseldorf, Nordrhein-Westfalen, Germany
JO

Julia Ortscheid

technical assistant
Department of Vascular- and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany
Duesseldorf, Nordrhein-Westfalen, Germany
TF

Tobias Feige

PhD Student
Department of Vascular- and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany
Duesseldorf, Nordrhein-Westfalen, Germany
SG

Simone Goressen

Postdoctoral Research Fellow
Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine University, Düsseldorf, Germany
Duesseldorf, Nordrhein-Westfalen, Germany
JF

Jens Fischer

Professor
Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine University, Düsseldorf, Germany
Duesseldorf, Nordrhein-Westfalen, Germany
ME

Margitta Elvers

Professor
Department of Vascular- and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany
Duesseldorf, Nordrhein-Westfalen, Germany

Background: Platelets play a critical role in acute myocardial infarction (AMI), influencing inflammation. Glycoprotein VI (GPVI), the major collagen receptor in platelets, is implicated in thrombus formation, but its comprehensive role in AMI remains unclear.

Aims: Study the role of GPVI deficiency on the outcome of myocardial infarction.

Methods: GPVI-deficient mice were utilized in a closed-chest AMI model. The closed-chest approach aimed to minimize surgery-induced inflammatory responses, with the left anterior descending artery (LAD) ligated for 60 minutes to induce cardiac damage. To determine left ventricular function, echocardiography was performed up to 21 days post AMI. Analysis of inflammatory markers via gene expression and cytokine array, as well as platelet-leukocyte-aggregates (PLA), was performed within the first 24 hours. The extent of cardiac remodeling from days 7 to 21 was assessed by gene expression analysis and IHC staining.

Results: GPVI deficiency did not influence acute inflammation 6 and 24 hours post-AMI, however, it significantly altered platelet function up to 24 hours post-AMI. Impaired platelet activation, particularly in response to PAR4 receptor stimulation, resulted in improved pro-coagulant activity measured via PS-exposure. This change correlated with decreased TGF-β plasma levels, while gene expression analysis revealed downregulation of Col1a1, Col3a1, Postn, and Cthrc1 seven days post-AMI. Consequently, collagen composition in the scar shifted towards a denser structure, altering scar formation and preserving cardiac function 21 days post-AMI.

Conclusion(s): This study highlights GPVI as a crucial regulator of platelet-induced cardiac remodeling in AMI. While GPVI deficiency does not affect acute inflammation, it significantly alters platelet function, leading to improved pro-coagulant activity and subsequent cardiac remodeling. The findings underscore the potential therapeutic relevance of GPVI as a target to mitigate ischemia-reperfusion injury and enhance cardiac healing after AMI. These insights contribute to a deeper understanding of platelet-mediated processes in AMI and offer avenues for better therapeutic strategies.