The elastase infusion model of experimental aortic aneurysms: synchrony of induction of endogenous proteinases with matrix destruction and inflammatory cell response.
OBJECTIVE
Perfusion of the isolated aorta of the rat with a saline solution containing pancreatic elastase induces an abdominal aortic aneurysm (AAA). An interesting feature of this model is the phenomenon of latency, suggesting that additional steps beyond the initial injury are required for AAA formation. This study was performed to determine whether the latency period for aortic dilation to aneurysmal proportions is correlated with the appearance of proteinases of endogenous origin and the interval for infiltration of inflammatory cells.


METHODS
Twenty Wistar rat aortas were perfused with the test solution, and 20 with normal saline solution. Laparotomy was performed on days 1, 2, 3, and 6 for measurement and harvest of the aorta. Histochemical studies were performed to analyze changes in matrix proteins, and substrate gel enzymography was used to determine the appearance of endogenous proteinases. Immunohistochemical studies were performed with monoclonal antibodies to T cells (CD-4, -5, and -8), monocytes/macrophages (ED-2), B cells (LC-A), immunoglobulin G, and immunoglobulin M.


RESULTS
The exogenously administered elastase was not detectable beyond day 2, but the aortic diameter did not progress to aneurysmal dimensions until the interval between days 3 and 6. During the period from day 3 to day 6, multiple endogenous matrix proteinases became detectable in the aortic tissue preparations. Immunohistochemical study revealed progressive infiltration of the aorta with various subsets of inflammatory cells.


CONCLUSIONS
The results suggest that the latency in AAA formation in this model corresponds with a complex sequence of biochemical and cellular events. The model provides an "early window" into these interesting early phases leading to aneurysm formation.
Department of Surgery, St. Luke's/Roosevelt Hospital Center, Columbia University, New York, NY 10019.
V J
VJ
Halpern
G B
GB
Nackman
R H
RH
Gandhi
E
E
Irizarry
J V
JV
Scholes
W G
WG
Ramey
M D
MD
Tilson
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D007249:Inflammation / Q000473:pathology; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D010450:Endopeptidases; D010196:Pancreatic Elastase