title: Aneurysm formation in proinflammatory, transgenic haptoglobin 2-2 mice.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurological Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Ruzevick
authors.forename: Christopher
authors.initials: C
authors.lastname: Jackson
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pradilla
authors.forename: Tomas
authors.initials: T
authors.lastname: Garzon-Muvdi
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Tamargo
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases / Q000235:genetics / Q000473:pathology; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006973:Hypertension / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000235:genetics* / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000502:physiology; D010196:Pancreatic Elastase / Q000494:pharmacology
chemical_list: D006242:Haptoglobins; D000804:Angiotensin II; D010196:Pancreatic Elastase