Annexin A7 (ANX7) regulates collagen-dependent platelet activation and Ca2+ signaling
S. Geue, B. Walker-Allgaier, D. Eißler, P. Münzer, F. Lang, M. Gawaz, O. Borst (1Tübingen, Germany)
Time: 11:00 - 12:00
Objective: Activation of platelets by subendothelial collagen results in an increase of cytosolic Ca2+ concentration ([Ca2+]i) and is followed by platelet secretion, aggregation and thrombus formation with consecutive vascular occlusion. This study aimed to determine the role of ANX7 in collagen-dependent platelet Ca2+ signaling and function in platelets from ANX7 knockout (anx7-/-) mice.
Methods: Fura-2-AM spectrofluorometric Ca2+ measurements, flowchamber and light transmission aggregometry were performed with platelets from ANX7 knockout mice.
Results: Stimulation of the collagen receptor glycoprotein VI (GPVI) by collagen or collagen-related peptide (CRP) leads to platelet activation due to increased intracellular calcium concentration ([Ca2+]i). Fura-2-AM spectrofluorometric Ca2+ measurements revealed that ANX7 deficiency strongly blunted Ca2+ mobilisation from intracellular stores and impaired extracellular Ca2+ influx in response to CRP and collagen. As platelet activation is linked with integrin αIIbβ3 activation and subsequent aggregation, light transmission aggregometry was performed uncovering a significant impaired platelet aggregation in anx7-/- platelets compared to anx7+/+ platelets after stimulation with CRP and collagen. Furthermore, GPIV-dependent platelet dense granule secretion (reflected by ATP release) as well as arterial thrombus formation under high shear rates (1700 s-1) on collagen were significantly diminished in anx7-/- platelets as compared to anx7+/+ platelets
Conclusion: In conclusion, ANX7 plays a pivotal role upon collagen-triggered platelet activation and thrombus formation at least due to impaired activation-dependent increase of [Ca2+]i.