Source of elastin-degrading enzymes in mycotic aortic aneurysms: bacteria or host inflammatory response?

Elastolytic matrix metalloproteinases play a central role in the development of chronic atherosclerotic aortic aneurysms, but mycotic aortic aneurysms are a distinct and unusual form of aneurysm disease caused by bacterial infection. Mycotic aortic aneurysms follow a more rapid and unpredictable course than chronic aneurysm disease and they exhibit a predilection for the suprarenal aorta, further implying unique pathophysiologic mechanisms. The purpose of this study was to examine the nature and source of elastin-degrading enzymes in mycotic aortic aneurysm. Bacterial isolates and aortic tissues were obtained from four consecutive patients undergoing surgical repair of suprarenal mycotic aortic aneurysm. Using an in vitro 3H-labeled elastin degradation assay, elastin-degrading enzyme activity was only observed in the bacteria-conditioned medium from an isolate of Pseudomonas aeruginosa. Elastin-degrading enzyme activity in the aortic tissue homogenate of this patient was abolished by the serine protease inhibitor, phenylmethylsulfonyl fluoride, but it was not suppressed by the metalloproteinase inhibitor, ethylenediamine tetraacetic acid (EDTA). In contrast, elastin-degrading enzyme activity in the bacterial-conditioned medium was decreased by about half by both phenylmethylsulfonyl fluoride and EDTA. Elastin substrate zymography revealed two phenylmethylsulfonyl fluoride-inhibitable elastin-degrading enzyme activities in the aortic tissue homogenate that corresponded to human neutrophil elastase (approximately 30 kDa) and its stable complex with alpha 1-proteinase inhibitor (approximately 80 kDa), but no activity attributable to Pseudomonas elastase, a 33-kDa metal-dependent enzyme. Human neutrophil elastase was readily detected throughout mycotic aortic aneurysm tissues by immunohistochemistry, but elastolytic metalloproteinases were only occasionally observed. The results of this study suggest that the elastin-degrading enzyme produced in mycotic aortic aneurysm are largely serine proteases of host neutrophil origin, rather than elastases produced by the infecting microorganisms or the macrophage-derived metalloproteinases typically observed in atherosclerotic aneurysm disease. Further studies will be needed to extend these findings to a larger number of patients with mycotic aortic aneurysm and those caused by additional microorganisms.