Abstract
In our previous study, we introduced the platelet endothelial cell adhesion molecule 1 (PECAM-1)/thrombus ratio, which is a parameter indicating the proportion of PECAM-1 in laser-induced thrombi in mice. Because PECAM-1 is an antithrombotic molecule, the higher the PECAM-1/thrombus ratio, the less activated the platelets. In this study, we used an extracorporeal model of thrombosis (flow chamber model) to verify its usefulness in the assessment of the PECAM-1/thrombus ratio in animal and human studies. Using the lipopolysaccharide (LPS)-induced inflammation model, we also evaluated whether the PECAM-1/thrombus ratio determined in the flow chamber (without endothelium) differed from that calculated in laser-induced thrombosis (with endothelium). We observed that acetylsalicylic acid (ASA) decreased the area of the thrombus while increasing the PECAM-1/thrombus ratio in healthy mice and humans in a dose-dependent manner. In LPS-treated mice, the PECAM-1/thrombus ratio decreased as the dose of ASA increased in both thrombosis models, but the direction of change in the thrombus area was inconsistent. Our study demonstrates that the PECAM-1/thrombus ratio can more accurately describe the platelet activation status than commonly used parameters such as the thrombus area, and, hence, it can be used in both human and animal studies.
Highlights
Platelet endothelial cell adhesion molecule 1 (PECAM-1) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily
Our study demonstrates that the combination of the PECAM‐1/thrombus ratio and flow chamber can be used in animal and human studies
Our study demonstrates that the combination of the PECAM-1/thrombus ratio and flow chamber can be used in animal and human studies
Summary
Platelet endothelial cell adhesion molecule 1 (PECAM-1) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily It is present on the surface of platelets, endothelial cells, monocytes, neutrophils, and lymphocytes [1]. PECAM-1 plays a pivotal role in the regulation of platelet activity by inhibiting the activation of receptors bearing an immunoreceptor tyrosine-based activation motif (ITAM). One such receptor is glycoprotein VI Fc receptor γ-chain (GPVI/FcR γ), which is the main collagen receptor in platelets. An immunoreceptor tyrosine-based inhibition motif (ITIM) is located on the cytoplasmic tail of PECAM-1. As a result of these motifs, Shp is located adjacent to phosphorylated ITAM and enables ITAM dephosphorylation, which inhibits the signaling pathway associated with platelet activation. PECAM-1 has been shown to suppress ADP- and thrombin-induced platelet activation, but the precise molecular mechanism underlying this process is unknown [2]
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