Aneurysm Formation in Proinflammatory, Transgenic Haptoglobin 2-2 Mice
ABSTRACT BACKGROUND:: Inflammation and macrophages in particular are believed to play a role in aneurysm formation. The haptoglobin (Hp) 2-2 genotype is associated with a pro-inflammatory state. OBJECTIVE:: To investigate the role of inflammation in the formation of aneurysms using a murine model of aneurysm formation in transgenic, pro-inflammatory, Hp2-2 mice and wild-type Hp1-1 mice. METHODS:: Carotid artery aneurysms (CCA) were induced in the left CCA of wild-type Hp1-1 mice and transgenic Hp2-2 mice using elastase to degrade the arterial wall of the CCA and angiotensin II to induce hypertension. There were four experimental groups: (1) sham surgery (n=11); (2) angiotensin II only (n=10); (3) elastase only (n=20); and (4) elastase + angiotensin II (n=20). Aneurysm size was determined by measuring the outer circumference and luminal circumference of the blood vessel. Macrophages that infiltrated the aneurysm wall were quantified by immunohistochemistry. Results were analyzed using a two-way ANOVA with a Bonferroni post-test. RESULTS:: Aneurysms in Hp-2-2 mice were significantly larger than aneurysms in Hp1-1 mice in the setting of vessel wall degradation and hypertension (p=0.02 for outer circumference, p=0.01 for luminal circumference). Furthermore, the number of macrophages infiltrating the aneurysm wall was significantly increased in Hp2-2 mice (p=0.0001). CONCLUSION:: Hp2-2 mice formed aneurysms that were significantly larger and had a significantly greater number of macrophages in the aneurysm wall as compared to Hp1-1 mice. This suggests the proinflammatory state associated with the Hp2-2 protein is involved in aneurysm formation, and suggests that Hp genotype may be a useful biomarker in predicting aneurysm progression.
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ABSTRACT: Fenestrations of intracranial arteries and associated aneurysms are rare. The significance of these fenestrations in relation to aneurysms remains unclear. We present four patients with fenestration-associated aneurysms and a comprehensive review of associations with aneurysms and other vascular lesions. A PubMed search of the literature was conducted from 1970-2012 reporting cases of intracranial aneurysms associated with arterial fenestration or duplications. Data were collected on patient presentation, sex, age, aneurysm and fenestration location, aneurysm treatment, and presence of other vascular lesions. We performed a retrospective review of four patients with intracranial fenestrations associated with aneurysms at our institution from 2012-2013. There were 59 cases of fenestrations and associated aneurysms in the literature. Aneurysms were reported as either arising from (n=50) or adjacent to but distinct from (n=13) fenestrations. The most common single fenestration location was at the basilar artery (n=23, 36.5%); however the majority of fenestrations were in the carotid circulation (n=34, 54.0%). The majority of patients with aneurysms and fenestrations at all locations except those at the anterior communicating artery (70.5%) presented with subarachnoid hemorrhage. Patients with aneurysms arising from a fenestration or adjacent to a fenestration presented with an additional intracranial vascular lesion in 38% and 31% of cases, respectively. The majority of all aneurysms were treated with microsurgical clipping. Aneurysms associated with cerebral arterial fenestrations are most commonly discovered after subarachnoid hemorrhage and are most often located in the carotid circulation. A high index of suspicion must be maintained for an associated vascular lesion if an intracranial fenestration is discovered.Journal of Clinical Neuroscience 08/2014; 21(12). DOI:10.1016/j.jocn.2014.07.005 · 1.32 Impact Factor
Neurosurgery 09/2013; 74(1). DOI:10.1227/NEU.0000000000000164 · 3.03 Impact Factor