Abstract
Background: Efferocytosis is an apoptotic cell clearing process that reduces the tissue-damaging effects of excessive apoptotic cells. Mer receptor tyrosine kinase (Mertk) is present on the surface of phagocyte cells, such as macrophages, and mediates efferocytosis of apoptotic cells. Cleavage of Mertk by metalloproteinases impairs efferocytosis. Several studies suggested that the severity of atherosclerosis, myocardial infarction, and aortic aneurysms were increased in Mertk KO mice due to the impairment of efferocytosis. Higher levels of apoptosis are found in ruptured aneurysms compared to in unruptured aneurysms, suggesting impaired efferocytosis in rupture-prone aneurysms. However, whether impaired efferocytosis plays a role in the pathophysiology of intracranial aneurysms is unclear. In this project, we investigated the effect of impaired efferocytosis in intracranial aneurysms.
Hypothesis: We hypothesize that impairment of efferocytosis promotes the rupture of intracranial aneurysms.
Methods: We induced intracranial aneurysms by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid in mice. Aneurysm rupture rate was used as the primary endpoint. We used Mertk knockout (KO) mice.
Results: There was no statistical difference in the formation rate of aneurysms between litter-mate control wild-type mice (WT) and Mertk KO mice. Interestingly, the aneurysmal rupture rate was significantly higher in Mertk KO mice (Mertk vs. WT: 94.7% vs. 61.5%, P < 0.05%).
Conclusions: Our experiment suggested that impairment of efferocytosis promotes aneurysm rupture. Inhibiting cleavage of Mertk may be a strategy for preventing the rupture of intracranial aneurysms.