Aneurysm growth, elastinolysis, and attempted doxycycline inhibition of elastase-induced aneurysms in rabbits.
OBJECTIVE
To establish the relationship between elastin degradation and aneurysm growth in New Zealand white rabbit model aneurysms, and to explore the potential for pharmacologic inhibition of elastinolysis and aneurysm growth with use of the matrix metalloproteinase (MMP) inhibitor doxycycline.


METHODS
Elastase-induced, saccular aneurysms created in the right common carotid artery in 30 animals randomly divided into controls (n = 16) and doxycycline treated (n = 14) were studied. Aneurysm growth was determined by angiography and aneurysm specimens were collected at 7 and 14 days for histologic and immunohistochemical analysis.


RESULTS
Aneurysms were characterized by marked elastin degradation and thickening of the arterial wall media in the absence of inflammatory cell markers. There was no evidence for expression of MMPs in the aneurysm wall at any time point. Aneurysm formation and growth were not prevented by the systemic administration of doxycycline. Mean aneurysm width increased from 3.1 +/- 0.7 mm at 3 days to 3.7 +/- 0.8 mm at 7 days and 4.2 +/- 0.8 mm at 14 days (P =.012 and P =.017, respectively). There was no statistically significant difference in aneurysm size and elastin content at any time point between doxycycline treated and control animals.


CONCLUSIONS
Elastase-induced rabbit aneurysm formation is accompanied by total elastin destruction that was not inhibited by the administration of doxycycline. Aneurysms in this model may be caused by the initial infusion of elastase, rather than by ongoing degradation from endogenous proteases released by inflammatory cells.
AAssar
O Sami
OS
Department of Radiology, University of Virginia HSC, 800170 Lee Street, Charlottesville, Virginia 22908, USA. olesami@carolina.rr.com
Fujiwara
Naomi H
NH
Marx
William F
WF
Matsumoto
Alan H
AH
Kallmes
David F
DF
D000818:Animals; D002340:Carotid Artery Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology*; D004549:Elastin / Q000378:metabolism*; D002532:Intracranial Aneurysm / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology*; D061965:Matrix Metalloproteinase Inhibitors; D010196:Pancreatic Elastase; D011817:Rabbits; D011897:Random Allocation
D061965:Matrix Metalloproteinase Inhibitors; D004549:Elastin; D010196:Pancreatic Elastase; D004318:Doxycycline