Aneurysm formation in proinflammatory, transgenic haptoglobin 2-2 mice

Jacob Ruzevick, Christopher Jackson, Gustavo Pradilla, Tomas Garzon-Muvdi, Rafael J. Tamargo

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)70-76
Number of pages7
JournalNeurosurgery
Volume72
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Keywords

  • Aneurysm formation
  • Haptoglobin
  • Inflammation
  • Macrophages

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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