Abstract 15: Pharmacological Activation of Efferocytosis Prevents Intracranial Aneurysm Rupture
Maeda, T; Take, Y; Uchikawa, H; Ishiguro, T; Ai, J; Eguchi, S; Lawton, M; Hashimoto, T
Published in: Stroke
Efferocytosis is the clearance process of dead or dying cells that reduces the tissue-damaging effects of excessive apoptotic cells. The accumulation of apoptotic cells at higher levels in ruptured aneurysms than in unruptured aneurysms suggests impaired efferocytosis. Mer receptor tyrosine kinase (MerTK), a receptor on macrophages, is essential for efferocytosis. Growth arrest-specific gene 6 (Gas6) is a small molecule that binds to and promotes MerTK-mediated efferocytosis. Our previous study suggested that MerTK knockout mice increased the rupture rate of intracranial aneurysms due to impaired efferocytosis. In this study, we investigated the effect of pharmacological activation of MerTK-mediated efferocytosis using the Gas6 in intracranial aneurysms.
We used 10-week-old male C57BL/6J mice. We induced intracranial aneurysms by a combination of elastase injection and hypertension. After aneurysm induction, we started treatment with Gas6 or PBS as a vehicle. We compared the aneurysm formation and rupture rates, and the survival curve between the two groups.
The aneurysm rupture rate was significantly lower in the Gas6 group than in the control group (85.0% versus 50.0%,
<0.05, Fig. A and B). There was no statistical difference in the rate of aneurysm formation between the Gas6 and control groups (80.0% versus 100%,
=0.07). The Gas6 group had a better survival rate than the control group (
<0.05, Fig. C).
Pharmacological activation of MerTK-mediated efferocytosis prevents intracranial aneurysm rupture. Our findings suggest that efferocytosis and MerTK may serve as novel therapeutic targets for the prevention of aneurysm rupture.
