By Thomas S. May
HELSINKI, FINLAND -- June 13, 2007 -- Treatment with rosiglitazone, a thiazolidinedione used for type II diabetes, is associated with plaque stabilization in symptomatic patients with unstable atherosclerotic plaques, according to new study presented here at the 76th Congress of the European Atherosclerosis Society (EAS).
The study evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic and symptomatic patients who underwent carotid endarterectomy. The investigators also assessed the effects of rosiglitazone on symptomatic plaques.
Symptomatic patients were given 8 mg rosiglitazone (n=20) or placebo (n=20) for 4 months before their scheduled endarterectomy. Plaques were subsequently collected and analysed for various markers of inflammation, such as T-lymphocytes (CD3), inflammatory cells (HLA-DR), as well as ubiquitin-proteasome activity, nuclear factor-kappa B (NF-kB) and collagen content.
An analysis of the results showed that, compared with placebo-treated plaques, rosiglitazone-treated symptomatic plaques had fewer inflammatory cells (P <.01), less ubiquitin, NF-kB (P <.01), and greater collagen content (P <.01), indicating a more stable plaque phenotype.
"Our research provides the missing link between thiazolidinedione therapy and NF-kB activity," said Raffaele Marfella, MD, PhD, professor, Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy. "The study demonstrates the inhibition of ubiquitin proteasome activity in human atherosclerotic lesions of symptomatic patients after rosiglitazone therapy and provides evidence that down-regulation of ubiquitin proteasome activity is associated with plaque stabilization, possibly by suppression of NF-kB-induced inflammation," he added.
"These findings are potentially important from a fundamental standpoint because they indicate a crucial role for the inhibition of ubiquitin proteasome activity in the stabilization of atherosclerotic lesions observed with thiazolidinediones," Dr. Marfella noted. "And from a practical standpoint, these findings provide further support for the possibility that thiazolidinediones might provide a novel form of therapy for plaque stabilization in patients with atherosclerotic disease."
This research was financially supported by GlaxoSmithKline, the manufacturers of rosiglitazone (Avandia®).
[Presentation title: Increased Activity of Ubiquitin-Proteasome System in Patients with Symptomatic Carotid Disease is Associated with Enhanced Inflammation: Effects of Rosiglitazone Treatment. Abstract P209]
E-Mail this DGDispatch to a colleague
