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Aneurysm Formation in Proinflammatory, Transgenic Haptoglobin 2-2 Mice

Ruzevick, Jacob BS; Jackson, Christopher BA; Pradilla, Gustavo MD; Garzon-Muvdi, Tomas MD; Tamargo, Rafael J. MD

Neurosurgery:
doi: 10.1227/NEU.0b013e318276b306
Research-Animal
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 proinflammatory state.

OBJECTIVE: To investigate the role of inflammation in the formation of aneurysms using a murine model of aneurysm formation in transgenic, proinflammatory Hp2-2 mice and wild-type Hp1-1 mice.

METHODS: Carotid artery aneurysms were induced in the left common carotid artery of wild-type Hp1-1 mice and transgenic Hp2-2 mice using elastase to degrade the arterial wall of the common carotid artery and angiotensin II to induce hypertension. There were 4 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 2-way analysis of variance with a Bonferroni post-test.

RESULTS: Aneurysms in Hp2-2 mice were significantly larger than aneurysms in Hp1-1 mice in the setting of vessel wall degradation and hypertension (P = .02 for outer circumference, P = .01 for luminal circumference). Furthermore, the number of macrophages infiltrating the aneurysm wall was significantly increased in Hp2-2 mice (P < .001).

CONCLUSION: Hp2-2 mice formed aneurysms that were significantly larger and had a significantly greater number of macrophages in the aneurysm wall compared with Hp1-1 mice. This suggests that the proinflammatory state associated with the Hp2-2 protein is involved in aneurysm formation and that the Hp genotype may be a useful biomarker in predicting aneurysm progression.

ABBREVIATIONS: AT II, angiotensin II

CCA, common carotid artery

Hp, haptoglobin

SAH, subarachnoid hemorrhage

Author Information

Department of Neurological Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Correspondence: Rafael J. Tamargo, MD, FACS, Division of Cerebrovascular Neurosurgery, The Johns Hopkins University School of Medicine, Sheikh Zayed Tower 6115G, The Johns Hopkins Hospital, 1800 Orleans St., Baltimore, MD 21287. E-mail: rtamarg@jhmi.edu

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Received May 1, 2012

Accepted September 14, 2012

Copyright © by the Congress of Neurological Surgeons