Related Experiment Video
Updated: Apr 7, 2026
Author Spotlight: Enhanced Murine AAA Model Using Elastase to Mimic Human Aneurysms
Published on: July 26, 2024
Paradoxical Increase in Mortality and Rupture of Intracranial Aneurysms in Microsomal Prostaglandin E2 Synthase Type
Ricardo A Peña Silva1, Ian J Mitchell, David K Kung
1*Universidad de los Andes, Bogotá, Colombia; ‡Departments of Internal Medicine, §Neurosurgery, ¶Microbiology, and ‖Pharmacology, University of Iowa, Iowa City, Iowa.
Background:
Inflammation plays an important role in formation and rupture of intracranial aneurysms. Expression of microsomal prostaglandin E2 (PGE2) synthase type 1 (mPGES-1) is increased in the wall of intracranial aneurysms in humans. PGE2, a by-product of mPGES-1, is associated with inflammation and cerebrovascular dysfunction.
Objective:
To test the hypothesis that deletion of mPGES-1 decreases the formation and rupture of intracranial aneurysms in a murine model.
Methods:
Intracranial aneurysms were induced in wild-type and mPGES-1 knockout (mPGES-1 KO) mice by using a combination of deoxycorticosterone acetate-salt-induced hypertension and intracranial injection of elastase in the basal cistern. Prevalence of aneurysms, subarachnoid hemorrhage, and mortality were assessed. We also tested the effects of administration of aspirin (6 mg/kg/d) by gavage and PGE2 (1 mg/kg/d) by subcutaneous infusion.
Results:
Systolic blood pressure and prevalence of aneurysm were similar in wild-type and mPGES-1 KO mice. However, mortality and the prevalence of subarachnoid hemorrhage were markedly increased in mPGES-1 KO mice (P < .05). Bone marrow reconstitution studies suggest that mPGES-1 derived from leukocytes does not appear to increase rupture of intracranial aneurysms. Aspirin, but not PGE2, attenuated the increased mortality in mPGES-1 KO mice (P < .05).
Conclusion:
Vascular mPGES-1 plays a protective role in blood vessels and attenuates rupture of cerebral aneurysms. In contrast to effects on abdominal aneurysms, mPGES-1 deficiency is associated with an increase in rupture of cerebral aneurysms and mortality, which are attenuated by low-dose aspirin.
Insights
Mice lacking microsomal prostaglandin E2 synthase type 1 (mPGES-1) showed increased mortality and subarachnoid hemorrhage, indicating mPGES-1 deficiency worsens cerebral aneurysm rupture. Low-dose aspirin mitigated these effects.
Area of Science:
- Cardiovascular Research
- Neuroscience
- Inflammation Biology
Background:
- Inflammation is key in intracranial aneurysm (IA) development and rupture.
- Microsomal prostaglandin E2 synthase type 1 (mPGES-1) expression is elevated in human IA walls.
- Prostaglandin E2 (PGE2), a product of mPGES-1, contributes to inflammation and cerebrovascular dysfunction.
Purpose of the Study:
- To investigate the role of mPGES-1 in IA formation and rupture.
- To test if mPGES-1 deletion exacerbates IA rupture in a murine model.
Main Methods:
- Intracranial aneurysms were induced in wild-type and mPGES-1 knockout mice via hypertension and elastase injection.
- Aneurysm prevalence, subarachnoid hemorrhage, and mortality were assessed.
- Effects of aspirin and PGE2 administration were evaluated.
Main Results:
- No significant difference in systolic blood pressure or aneurysm prevalence between groups.
- Markedly increased mortality and subarachnoid hemorrhage prevalence in mPGES-1 knockout mice.
- Aspirin, but not PGE2, reduced mortality in mPGES-1 knockout mice.
Conclusions:
- Vascular mPGES-1 plays a protective role against cerebral aneurysm rupture.
- mPGES-1 deficiency increases cerebral aneurysm rupture and mortality, contrary to effects on abdominal aneurysms.
- Low-dose aspirin can attenuate the increased rupture and mortality associated with mPGES-1 deficiency.
