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
SAH, subarachnoid hemorrhage
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: email@example.com
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.neurosurgery-online.com).
Received May 1, 2012
Accepted September 14, 2012