Reduced protease inhibitory capacity in patients with abdominal aortic aneurysms is reversed with surgical repair.
BACKGROUND
Abdominal aortic aneurysm (AAA) disease is a complex degenerative process that is associated with elevated proteolytic activity. This increased proteolytic activity may be linked to an imbalance in the protease regulatory mechanisms. We hypothesize that reduced AAA plasma inhibitory capacity is related to increased elastolytic activity observed in patients with AAA, which promotes matrix degradation in the aortic wall and AAA expansion.


METHODS
Preoperative plasma from patients with AAA (n = 86; mean age, 75 +/- 8 years) and healthy controls (n = 30; mean age, 72 +/- 10 years) was assayed for inhibitory capacity. Postoperative plasma inhibitory capacity was evaluated with comparison of the activity of porcine pancreatic elastase on succinylated elastin substrate, in the presence and absence of AAA and control plasma.


RESULTS
AAA plasma showed a significantly reduced capacity to inhibit porcine pancreatic elastase (71.31% +/- 1.47%) compared with control plasma (85.52% +/- 1.70%; P <.001). Within the AAA group, the inhibitory capacity increased with AAA diameter (P <.05). In addition, surgical repair of AAA resulted in a significant increase in plasma inhibitory capacity (79.83% +/- 1.86%) as compared with preoperative levels (63.98% +/- 2.69%; P <.001). Of note, the postoperative plasma inhibitory capacity is not significantly different than that of control.


CONCLUSIONS
AAA plasma has a significantly reduced inhibitory capacity, which varies with aortic diameter and returns to control levels after surgical repair of the AAA. This suggests that protease regulation is a dynamic balance that changes with AAA progression and may play an important role in AAA progression.
Halpern
Vivienne J
VJ
Department of Surgery, Division of Vascular Surgery, Long Island Jewish Medical Center, Long Island Campus of the Albert Einstein College of Medicine, North Shore-LIJ Health System, New Hyde Park, NY 11040, USA. halpern@lij.edu
Mathrumbutham
Mahesh
M
Lagraize
Christopher
C
Rao
Srinvasa K
SK
Faust
Glenn R
GR
Cohen
Jon R
JR
D000368:Aged; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000601:surgery*; D016022:Case-Control Studies; D006801:Humans; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000378:metabolism*; D012907:Smoking / Q000453:epidemiology; D013552:Swine
D011480:Protease Inhibitors; D010196:Pancreatic Elastase