Aneurysm Formation in Proinflammatory, Transgenic Haptoglobin 2-2 Mice

The Johns Hopkins University School of Medicine, Department of Neurological Surgery, Baltimore, MD, USA.
Neurosurgery (Impact Factor: 3.62). 10/2012; 72(1). DOI: 10.1227/NEU.0b013e318276b306
Source: PubMed


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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