There is strong epidemiological evidence that patients with diabetes have a lower incidence of abdominal aortic
aneurysm. The precise mechanism of this negative association is unknown. Whilst a number of studies have supported the
hypothesis that protection is a function of diabetes-mediated changes in the vascular extracellular matrix biology, there is
also support for the idea that the treatment regimens used in diabetes may afford protection against AAA. In particular the
pleiotropic drug family, the thiazolidinediones have been examined as candidates to ameliorate aneurysm formation. Both
the thiazolidinediones, and the structurally related family, fibrates, have been shown to have anti-inflammatory and antioxidative
effects, in addition to ability to modulatate glucose and lipid homeostasis. In this brief review we present the
current data exploring the use of thiazolidinediones in experimental aneurysm development. Despite the fact that both thiazolidinediones
Rosiglitazone and Pioglitazone are no longer prescribed in Europe and the US, they have provided important
insights into the mechanism of action, and the application of other pleiotropic drugs in the treatment of AAA. One
such pleiotropic drug is high-density lipoproteins (HDLs), which have been shown to have a broad spectrum of effects,
including activation of PPARs, which may favour their use as a new drug target for protection against AAA development.
Keywords: Aneurysms, diabetes, fibrates, high-density lipoproteins, peroxisome proliferator-activator receptors, thiazolidinediones.
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