Indomethacin inhibits expansion of experimental aortic aneurysms via inhibition of the cox2 isoform of cyclooxygenase Manuel Miralles, MD, William Wester,

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Presentation transcript:

Indomethacin inhibits expansion of experimental aortic aneurysms via inhibition of the cox2 isoform of cyclooxygenase Manuel Miralles, MD, William Wester, BS, Gregorio A. Sicard, MD, Robert Thompson, MD, Jeffrey M. Reilly, MD Journal of Vascular Surgery Volume 29, Issue 5, Pages 884-893 (May 1999) DOI: 10.1016/S0741-5214(99)70216-8 Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig 1 Graphic representation of aortic diameters in each group with time. Note that the elastase-only and indomethacin groups are nearly identical until day 4. Also, saline perfusion alone has little effect on aortic diameter. Journal of Vascular Surgery 1999 29, 884-893DOI: (10.1016/S0741-5214(99)70216-8) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig 2 Graphic representation of prostaglandin E2 (PGE2) synthesis with time. Note that saline perfusion had little effect, whereas in the elastase-only and indomethacin groups, PGE2 synthesis mirrored aortic dilatation, with peak synthesis noted on day 14, when aortic dilatation was maximal. By day 28, PGE2 was nearly back to baseline, and all aortic dilatation had stopped. Journal of Vascular Surgery 1999 29, 884-893DOI: (10.1016/S0741-5214(99)70216-8) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig 3 Zymogram of aortic culture medium taken at day 14. On the right is a sample from a saline-perfused aorta (saline), the next three lanes (elastase) are from the elastase-only group, and the last three lanes (Indo) are indomethacin-treated aortas. The band at 92 kDa represents matrix metalloprotease-9 (MMP-9). In the saline group, there is minimal MMP-9 activity. In the elastase-only group, there is significant lytic activity from MMP-9, and in the indomethacin group, MMP-9 activity is comparable to baseline. This indicates that indomethacin is associated with decreasing MMP-9 activity. Journal of Vascular Surgery 1999 29, 884-893DOI: (10.1016/S0741-5214(99)70216-8) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig 4 Aortic tissue that has been stained with Verhoeff-van Gieson stain. The elastin fibers stain black within the media. Both micrographs were taken of aortas harvested on day 4. On the left is an elastase-only specimen, and on the right is a specimen from an animal treated with indomethacin. There is little difference in the architecture of the media between the two aortas at this point. Journal of Vascular Surgery 1999 29, 884-893DOI: (10.1016/S0741-5214(99)70216-8) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig 5 Aortic tissue similar to that shown in Fig 4, except these aortic specimens are from day 28. On the left is an elastase-only specimen that shows nearly complete loss of elastin fibers within the media. In the indomethacin-treated aorta, there is an obvious loss of elastin fibers within the media. In the indomethacin-treated aorta, there is obvious loss of elastin integrity, but much of the elastin is still intact, indicating that indomethacin helps minimize damage to elastin in this model. Journal of Vascular Surgery 1999 29, 884-893DOI: (10.1016/S0741-5214(99)70216-8) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig 6 Photomicrograph from an elastase-treated aorta, harvested on day 14, that has been immunostained for cox2. Note the cell-specific hybridization within macrophages in the inflammatory infiltrate. Journal of Vascular Surgery 1999 29, 884-893DOI: (10.1016/S0741-5214(99)70216-8) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig 7 Photomicrograph of an in situ hybridization for cox2 on an elastase-only aorta harvested on day 14. Once again, note the cell-specific hybridization within macrophages in the inflammatory infiltrate. Journal of Vascular Surgery 1999 29, 884-893DOI: (10.1016/S0741-5214(99)70216-8) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions