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. 2023:1408:65-82.
doi: 10.1007/978-3-031-26163-3_4.

α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6

Felipe M Llancalahuen  1   2 , Alejando Vallejos  1   2 , Diego Aravena  1   2 , Yolanda Prado  1   2 , Sebastian Gatica  1   2 , Carolina Otero  3 , Felipe Simon  4   5   6
Affiliations

α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6

Felipe M Llancalahuen et al. Adv Exp Med Biol. 2023.

Abstract

Stimulation of a1-adrenergic nervous system is increased during systemic inflammation and other pathological conditions with the consequent adrenergic receptors (ARs) activation. It has been reported that a1-stimulation contributes to coagulation since a1-AR blockers inhibit coagulation and its organic consequences. Also, coagulation induced by a1-AR stimulation can be greatly decreased using a1-AR blockers. In health, endothelial cells (ECs) perform anticoagulant actions at cellular and molecular level. However, during inflammation, ECs turn dysfunctional promoting a procoagulant state. Endothelium-dependent coagulation progresses at cellular and molecular levels, promoting endothelial acquisition of procoagulant properties to potentiate coagulation by means of prothrombotic and antifibrinolytic proteins expression increase in ECs releasing them to circulation, the thrombus formation is strengthened. Calcium signaling is a main feature of coagulation. Inhibition of ion channels involved in Ca2+ entry severely decreases coagulation. The transient receptor potential canonical 6 (TRPC6) is a non-selective Ca2+-permeable ion channel. TRPC6 activity is induced by diacylglycerol, suggesting that is regulated by a1-ARs. Furthermore, a1-ARs stimulation elicits a TRPC-like current in rat mesenteric artery smooth muscle and mesangial cells. However, whether TRPC6 could promote an ECs-mediated platelet adhesion induced by a1-adrenergic stimulation is currently not known. Therefore, the aim of this study was to examine if the TRPC6 calcium channel mediates platelet adhesion induced by a1-adrenergic stimulation. Our results suggest that platelet adhesion to ECs is enhanced by the a1-adrenergic stimulation evoked by phenylephrine mediated by TRPC6 activity. We conclude that TRPC6 is a molecular determinant in platelet adhesion to ECs with implications in systemic inflammatory diseases treatment.

Keywords: Calcium; Endothelial cells; Platelet adhesion; TRPC6; α1-adrenergic receptor.

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