Thiazolidenediones and aneurysmal disease

Background

Abdominal aortic aneurysms (AAAs), are a chronic degenerative pathology primarily affecting elderly males with a prevalence of 5%.Although the precise mechanism of genesis is unknown, development of the lesion involves inflammation, thrombogenesis, apoptosis, oxidative processes and matrix modulation.The ability to stabilise or regress such a complex pathology may depend on a pharmacoptherapeutic agent with a broad spectrum of effects.We evaluated the ability of Roziglitazone, a peroxisome proliferator-activator receptor (PPAR) agonist with a broad spectrum of effects, to inhibit the development of experimental aortic aneurysm.

Methods

To test the effects of Rosiglitazone, thirty 12-month-old ApoE-/-/C57B16 mice were randomised into three groups.All animals were inserted with an osmotic pump subcutaneously.The positive control group and treatment group released Angiotensin II (Ang-II) (1mg/min/Kg), the negative control group released saline and the treatment group received Rosiglitazone (10mg/kg/day) in their drinking water daily for one week before inserting the pumps and continuously thereafter for 28 days.At 28 days aortic area was evaluated by MRI scanning and animals dissected to isolate tissue for histology and mRNA expression analysis.

Results

In comparison to the positive control group, treatment with Rosiglitazone inhibited the occurrence of fatal rupture (5/10 vs. 0/10) and reduced mean maximal aortic dilatation (0.063+/-0.002 vs. 0.042+/-0.002, p<0.009).Mean maximal aortic area calculated using MRI imaging correlated with that calculated using computer assisted histological sectioning (r=0.9).

Conclusion

Rosiglitazone (a PPARgamma agonist) reduces aneurysm development and rupture in a murine model.