A failure of matrix metalloproteinase inhibition in the prevention of rat intracranial aneurysm formation
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We tested the hypothesis that nonspecific matrix metalloproteinase (MMP) inhibition with doxycycline would decrease the incidence of intracranial aneurysm formation in a rat aneurysm model. We performed common carotid artery ligation on 96 Long-Evans rats. A treatment group of 48 animals was chosen at random to receive oral doxycycline (3 mg/kg) in addition to standard rat chow, and the control group of 48 animals received standard rat chow only. The major circle of Willis arteries was dissected at 1 year following carotid ligation, and the proportions of animals with aneurysms were compared between groups using Fisher’s exact test. Four animals given oral doxycycline and ten control animals expired before 1 year. Of the examined animals, eight saccular intracranial aneurysms were found in 8 of 45 animals which had received doxycycline (17.8%) and seven saccular intracranial aneurysms were found in 7 of 37 control animals (18.9%). There was no significant difference in aneurysm formation between the doxycycline-treated and control groups (P=0.894). Nonspecific MMP inhibition with doxycycline is not effective in preventing intracranial aneurysm formation in a rat model.
KeywordsIntracranial aneurysm Animals Matrix metalloproteinases
A Radiological Society of North America Research Resident Grant supported this work. This work was performed in the Department of Radiology, University of Virginia, Charlottesville, VA, USA. We sincerely thank Kevin S. Lee, Ph.D., University of Virginia, for invaluable advice and assistance in perfusion-fixation.
- 2.Baxter BR, Pearce WH, Waltke EA, Littooy FN, Hallett JW, Kent KC, Upchurch GR, Chaikof EL, Mills JL, Fleckten B, Longo GM, Lee JK, Thompson RW (2002) Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (phase II) multicenter study. J Vasc Surg 36:1–12PubMedCrossRefGoogle Scholar
- 24.Petrinec D, Liao S, Holmes DR, Reilly JM, Parks WC, Thompson RW (1996) Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: preservation of aortic elastin associated with suppressed production of 92 kD gelatinase. J Vasc Surg 23:336–346PubMedCrossRefGoogle Scholar
- 25.Pyo R, Lee JK, Shipley JM, Curci JA, Mao D, Ziporin SJ, Ennis TL, Shapiro SD, Senior RM, Thompson RW (2000) Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest 105:1641–1649PubMedCrossRefGoogle Scholar