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Doxycycline treatment in a model of early abdominal aortic aneurysm
Keiko Kaito1, Hiroshi Urayama, Go Watanabe
1Department of General and Cardiothoracic Surgery, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Purpose:
To evaluate the effects doxycycline (Dox) in animal models of early abdominal aortic aneurysm.
Methods:
Of 43 male Wistar rats, 33 underwent intraluminal perfusion of the abdominal aorta with thioglycolate plus plasmin to reproduce early aortic aneurysm. These rats then were treated for 7 days with subcutaneous injections of Dox or saline. The 10 remaining rats underwent intra-aortic perfusion with saline and were injected subcutaneously with saline. On day 7, the rats were killed after abdominal aortic diameters were measured. Some aortic specimens were examined microscopically after elastica van Gieson (EVG) and hematoxylin-eosin (H&E) staining. In other specimens, the matrix metalloproteinase (MMP) activity in tissue extracts was evaluated by gelatin zymography.
Results:
Among the thioglycolate plus plasmin-perfused rats, the degree of aortic dilation was less in Dox-treated than in saline-treated rats. EVG staining indicated that Dox maintained a nearly normal pattern of elastic lamellae and normal medial elastin thickness. The aortic inflammatory response was not suppressed by Dox in H&E staining. In gelatin zymography, Dox reduced the MMP-9 activity, but did not significantly change either MMP-2 or the percentage of activated MMP-2.
Conclusions:
Dox inhibited experimental aneurysmal dilation by preserving medial elastin. This effect involved the suppression of MMP-9 but not of the MMP-2 activity.