Abstract 170: Aspirin Reduces Mortality Caused by Intracranial Aneurysm Rupture in mPGES-1 Deficient Mice
Inflammation plays an important role in formation and rupture of intracranial aneurysms. Prostaglandin (PG) E2, a by-product 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 knockout (KO) and wild-type (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. All WT mice survived 3 weeks after surgery and did not develop signs of subarachnoid hemorrhage (SAH). The majority of WT mice [73% (8/11)] 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 (P<0.05). 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. Subcutaneous infusion of PGE2 (1 mg/kg/d) to mPGES-1 KO mice did not appear to attenuate mortality or intracranial aneurysm rupture (p>0.05). Another group of mPGES-1 KO mice were treated with aspirin (6 mg/kg/d) or vehicle (water) by gavage since day 2 after surgery. Mortality caused by symptomatic aneurysm rupture was significantly reduced in aspirin (25% (3/12) vs vehicle (58% (7/12)) treated mPGES-1 KO mice (P<0.05). 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. Aspirin treatment significantly reduced mortality in mPGES-1 KO mice (P<0.05). Therefore, mPGES-1 and aspirin appear to play a protective role against rupture of intracranial aneurysms in mice.
Author Disclosures: R.A. Pena SIlva: None. D. Kung: None. I.J. Mitchell: None. F.M. Faraci: None. D.D. Heistad: None. D. Hasan: None.
- © 2014 by American Heart Association, Inc.