Key result
Platelet GPVI depletion reduces post-MI collagen deposition and CLEC-2 depletion improves survival in mice.
Why the study?
The nature and functional outcomes of platelet and immune cell interactions had not been elucidated in ischemic heart disease.
Answers are grounded in this paper and cite their sources.
Platelets interact with immune cells after myocardial infarction, affecting their gene expression and function, and emerge as possible inflammatory triggers in post-MI cardiac repair.
Myocardial Infarction (MI) is one of the leading causes of mortality worldwide and is tightly associated with left ventricular remodeling, worsening of cardiac function and development of heart failure (HF). Immune cells (ICs) play a dual role following MI as they contribute to both tissue damage and repair. Platelets are the main mediators of hemostasis and thrombosis and can interact both directly and via paracrine effects with ICs, triggering their activation and recruitment to inflammatory sites. The presence of circulating platelet/IC conjugates has been reported in MI patients. Nevertheless, the nature of platelet/IC interaction and its functional outcomes have not been elucidated in ischemic heart disease yet. The aim of this thesis is to investigate the interaction between platelets and ICs in the context of post MI cardiac repair. Using fluorescence microscopy, the direct interaction of platelets with macrophages, neutrophils and monocytes in various phases of post MI cardiac repair was visualized. A co-culture in vitro system, where bone marrow derived macrophages were cultured together with platelets (resting or activated with thrombin) was developed. Bulk RNA-sequencing of macrophages treated with activated platelets showed upregulation of genes associated with inflammation, angiogenesis and response to hypoxia. These effects were mostly contact dependent with the platelet paracrine effects playing a minor role. In a model of permanent MI in mice, blockade or depletion of platelet glycoprotein (GP) receptors GPIb, GPVI, GPIIb/IIIa and CLEC-2 did not affect inflammatory cell accumulation in the infarcted heart. However, depletion of platelet GPVI led to decreased collagen deposition, while CLEC-2 depletion improved mice survival. Altogether, our work shows that platelets interact with ICs after MI, affecting their gene expression and function. Thus, platelets are emerging as possible inflammatory triggers in the context of post MI cardiac repair.
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Anna Rizakou (2024) studied Myocardial Infarction. Blockade or depletion of platelet glycoprotein receptors (GPIb, GPVI, GPIIb/IIIa, CLEC-2) was evaluated on Inflammatory cell accumulation, collagen deposition, and survival. In a mouse model of myocardial infarction, platelets interacted with immune cells, with GPVI depletion decreasing collagen deposition and CLEC-2 depletion improving survival.
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