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Rapamycin suppresses experimental aortic aneurysm growth
David M Lawrence1, Robert S Singh, David P Franklin
1Section of Vascular Surgery and Weis Center for Research, Geisinger Clinic, Danville, PA 17822, USA.
Journal of Vascular Surgery
|August 7, 2004
Summary
Rapamycin treatment significantly reduced abdominal aortic aneurysm (AAA) expansion in a rat model. This immunosuppressive drug suppressed inflammation and matrix metalloproteinase-9, offering potential for treating small aneurysms.
Area of Science:
- Vascular Biology
- Immunology
- Pharmacology
Background:
- Abdominal aortic aneurysms (AAAs) involve inflammatory processes.
- Gene expression profiling identified FK506BP12 (rapamycin binding protein) as upregulated in AAA tissue.
- Rapamycin, an immunosuppressant, has not been studied for its effects on aneurysm formation.
Purpose of the Study:
- To investigate the therapeutic potential of rapamycin in an experimental rat model of AAA.
- To determine if rapamycin can inhibit aneurysm development and expansion.
Main Methods:
- Experimental AAAs were induced in Wistar rats using elastase infusion.
- Rats received daily rapamycin or placebo via gastric lavage post-surgery.
- Aneurysm diameter, NF-kappa B activation, MMP-9 levels, and tissue histology were assessed on postoperative day 7.
Main Results:
- Rapamycin treatment significantly reduced aneurysm diameter by 40% (3.3 +/- 0.7 mm vs. 4.5 +/- 0.5 mm).
- NF-kappa B activation (inflammation marker) was reduced by 64% in rapamycin-treated aortas.
- MMP-9 levels decreased by 54% in rapamycin-treated aortas, with no significant changes in inflammatory infiltrate or elastin degradation.
Conclusions:
- Rapamycin effectively suppresses aneurysm expansion in a rat AAA model.
- The mechanism involves the suppression of inflammatory signaling pathways and reduced MMP-9 activity.
- Rapamycin shows promise as a novel therapeutic agent for managing small aneurysms.