Abstract Number: PB1737
Meeting: ISTH 2020 Congress
Background: Cardiovascular diseases (CVD) are the main causes of mortality in the world. A common element in CVD is thrombus formation, mostly composed of platelets.
Platelets participating in hemostasis and the innate immune system. In particular, platelets release cytokines and express pro-inflammatory receptors.
In this context, the presence of the Receptor for Advanced Glycation End-products (RAGE) during the development of CVD has been recently described. RAGE is a pattern recognition receptor and is capable of potentiating the progression of atherothrombosis.
However, it is not yet clear what is the role of RAGE in platelet functionality.
Aims: To evaluate the role of RAGE activation in human platelet functionality.
Methods: Human platelets were collected from healthy volunteers. We analyze the presence of RAGE by flow cytometry. The platelet function was evaluated in vitro by lumiagregometry and P-selectin exposure. In addition, RAGE-mediated intra-platelet signaling was evaluated by western blot. Finally, the agonist and inhibitor interaction with RAGE was determined in silico. The statistical analysis T-Test was carried out with Prism 6.0c.
Results: We found a mean fluorescence intensity (MFI) of RAGE on resting platelet was 2236±481 and increased significantly in stimulated platelets (4390±1087).
In addition, RAGE stimulation with AGE-BSA activated NFkB signaling and increase the platelet aggregation (58.50±7.8) and exposure of P-selectin (3402±844.1 of MFI). This effects are blocked by RAGE inhibitor.
Finally, we were able to predict that the region stimulated by AGE-BSA is located in region V of RAGE and also 13 amino acids are critical for its binding.
Conclusions: In conclusion, we confirmed the presence of RAGE in human platelets. The activation of RAGE causes changes in platelet functionality such as increased aggregation and activation by NFkB signaling. In addition, we predicted the critical region for its stimulation. This information is crucial for in the future to propose possible treatments for CVD.
To cite this abstract in AMA style:Recabarren-Leiva D, Wehinger S, Fuentes E, Palomo I, Alarcón M. Role of Receptor for Advanced Glycation End-products (RAGE) in Human Platelets [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/role-of-receptor-for-advanced-glycation-end-products-rage-in-human-platelets/. Accessed January 21, 2022.
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