Skip to main content
  • Role of the Haptoglobin protein in carotid artery aneurysm formation

    Final Number:

    Jacob James Ruzevick; Christopher Mitchell Jackson; Gustavo Pradilla MD; Tomas Garzon-Muvdi MD MS; Rafael J. Tamargo MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2012 Annual Meeting

    Introduction: Previous clinical studies have found an association between the serum protein, haptoglobin (Hp), and the formation of abdominal aneurysms, but no studies have investigated this association in a physiologically relevant, preclinical model of aneurysm formation. We investigated the size of aneurysms in wild-type Hp1-1 and pro-inflammatory Hp2-2 mice and found the Hp2-2 genotype to be associated with increased aneurysm size and increased numbers of macrophages infiltrating the vessel wall.

    Methods: Carotid artery aneurysms (CCA) were induced in the left CCA of wild-type Hp1-1 mice and transgenic Hp2-2 mice using a physiologically relevant aneurysm model that involves administration of elastase to cause vessel wall destruction and angiotensin II to cause 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). The size of all aneurysms was determined by measuring the outer circumference and luminal circumference. Macrophages that infiltrated the aneurysm wall were quantified by immunohistochemistry. All results were analyzed using a two-way ANOVA with a Bonferroni post-test.

    Results: Concomitant administration of elastase and angiotensin II resulted in a significant increase in aneurysm size as compared to all other treatment groups. Using this model, we found that aneurysms in Hp-2-2 mice were significantly larger than aneurysms in Hp1-1 mice (p=0.02 for outer circumference, p=0.0006 for inner circumference)(Figure 1 and Figure 2). Finally, the number of infiltrating macrophages was significantly increased in aneurysms in Hp2-2 mice in the setting of vessel wall destruction and hypertension (p=0.0001) (Figure 3).

    Conclusions: Hp2-2 mice formed aneurysms that were significantly larger and had a significantly increased number of macrophages in the aneurysm wall as compared to Hp1-1 mice. This suggests that the Hp protein is involved in aneurysm formation and that Hp genotype may be a useful biomarker in predicting aneurysm progression.

    Patient Care: Currently there is no biomarker to follow or predict aneurysm growth. Our data suggests that a patients' haptoglobin genotype, specifically the Hp2-2 genotype, is associated with increased aneurysm growth which may alter treatment decisions.

    Learning Objectives: By the conclusion of this session, participants should be able to: (1) discuss the factors involved in aneurysm formation; (2) describe the importance of a pro-inflammatory state on aneurysm formation and; (3) discuss the possibility of the haptoglobin protein as a biomarker for increased aneurysm growth.

    References: 1. Hoh BL, Velat GJ, Wilmer EN, Hosaka K, Fisher RC, Scott EW. A novel murine elastase saccular aneurysm model for studying bone marrow progenitor-derived cell-mediated processes in aneurysm formation. Neurosurgery. Mar 2010;66(3):544-550; discussion 550. 2. Wiernicki I, Safranow K, Baranowska-Bosiacka I, Piatek J, Gutowski P. Haptoglobin 2-1 phenotype predicts rapid growth of abdominal aortic aneurysms. J Vasc Surg. Sep 2010;52(3):691-696. 3. Kadirvel R, Ding YH, Dai D, Lewis DA, Kallmes DF. Differential expression of genes in elastase-induced saccular aneurysms with high and low aspect ratios. Neurosurgery. Mar 2010;66(3):578-584; discussion 584. 4. Wiernicki I, Safranow K, Baranowska-Bosiacka I, Piatek J, Gutowski P. Haptoglobin 2-1 phenotype predicts rapid growth of abdominal aortic aneurysms. J Vasc Surg. Sep 2010;52(3):691-696.

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy