MPGES‐1 deficiency increases mortality and aneurysm rupture in a mouse model of intracranial aneurysms

Abstract

Studies in humans and mice suggest that inflammation plays an important role in formation and rupture of intracranial aneurysms. Prostaglandin (Pg) E2, a byproduct of microsomal prostaglandin E2 synthase (mPGES)‐1, is associated with inflammation and cerebrovascular dysfunction. We hypothesized that mPGES‐1 deficiency protects against rupture of intracranial aneurysms. Intracranial aneurysms were induced in mPGES‐1 KO and WT mice with DOCA‐salt hypertension and an intracranial injection of elastase. Systolic blood pressure and water intake (1% saline) was similar in WT and mPGES‐1 KO mice. Body weight did not change in any group during the experiment. All WT mice survived 3 weeks after the surgery and did not develop signs of subarachnoid hemorrhage (SAH). 73% (8/11)of WT mice developed aneurysmal dilatations in the cerebral arteries without evidence of SAH. In contrast, half of mPGES‐1 deficient mice died or showed signs of SAH during follow‐up. Postmortem analysis showed SAH in 56% (9/16)of mPGES‐1 deficient mice. Unruptured aneurysms with no evidence of SAH were found in 25% (4/16)of mPGES‐1 deficient mice. In conclusion, we found that genetic deficiency of mPGES‐1 is associated with increased aneurysm rupture (p<0.01)and mortality (p<0.05) in a mouse model of intracranial aneurysms. mPGES‐1 appears to play a protective role against rupture of intracranial aneurysms in mice.