Elastase is not sufficient to induce experimental abdominal aortic aneurysms.
OBJECTIVE
Research investigating abdominal aortic aneurysms (AAAs) commonly uses a rat model dependent on aortic infusion of porcine pancreatic elastase to initiate AAA formation. Unfortunately, the sizes of AAAs generated by this model have varied widely among published studies. This may reflect lot-to-lot variations in commercial elastase preparations. This study was undertaken to investigate the ability of different lots of elastase to induce AAAs and explain the variability identified.


METHODS
Four lots of elastase were evaluated in the standard rat AAA model. Saline solution was used as a control. Additional groups of rats were treated with higher concentrations of elastase with or without the macrophage activator thioglycollate medium. Aortic diameters were measured in all rats. Inflammation and elastin degradation was examined histologically. Elastase activity and purity were evaluated for all lots.


RESULTS
Of the four lots tested, only one was able to consistently generate AAAs at the standard dose (P <.05). Increasing the amount of elastase infused produced AAAs in some ineffective lots. Infusion of thioglycollate medium in combination with otherwise ineffective elastase produced AAAs (P =.02). However, the elastase with the highest purity failed to generate AAAs, even at the highest dose tested or in combination with thyioglycollate medium. Thioglycollate medium alone failed to result in AAA formation. All elastase lots displayed elastolytic activity in vitro and produced elastin degradation in vivo. Elastin degradation did not correlate with AAA size in elastase-treated rats (P = NS). Aneurysm size correlated with extent of inflammation (P =.005).


CONCLUSIONS
Induction of AAAs does not correlate with elastolytic activity. Infusion of pure elastase alone is not sufficient to induce AAA formation in spite of evidence of elastin degradation. Presumed inflammatory modifiers, which contaminate some elastase preparations, enhance AAA formation. Future use of this rat model will need to take the variability of elastase preparations into account with controls for each new elastase lot.
Carsten
C G
CG
Section of Vascular Surgery and Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pa 17822-2150, USA.
Calton
W C
WC
Johanning
J M
JM
Armstrong
P J
PJ
Franklin
D P
DP
Carey
D J
DJ
Elmore
J R
JR
D000704:Analysis of Variance; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced* / Q000473:pathology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D007262:Infusions, Intravenous; D016014:Linear Models; D008297:Male; D010196:Pancreatic Elastase / Q000145:classification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D013864:Thioglycolates / Q000494:pharmacology; D014657:Vasculitis / Q000473:pathology*
D013864:Thioglycolates; D010196:Pancreatic Elastase