Rosiglitazone Reduces the Inflammatory Response in a Model of Vascular Injury in Rats

Abstract

Thiazolidinediones are ligands that bind to and activate the nuclear peroxisome proliferator-activated receptor gamma. They are widely used as insulin sensitizers for the treatment of type 2 diabetes. Several studies have implicated the peroxisome proliferator-activated receptor gamma agonists rosiglitazone and pioglitazone in inflammatory events. To assess the anti-inflammatory properties of rosiglitazone, we investigated its effects on the molecular and cellular inflammatory response induced by a carotid injury in the rat. Male Wistar rats were randomized into a rosiglitazone-treated group (10 mg kg(-1) day(-1)) and a control group (0.9% w/v NaCl). The drug or vehicle was administered by gavage for 7 days before carotid injury and for up to 21 days after injury. The inflammatory markers p38 mitogen-activated protein kinase, cyclooxygenase 2, nuclear factor-kappaB, and heat shock protein 47 and the influx and activity of cells in response to injury were measured. Rosiglitazone treatment significantly reduced the expression of the inflammatory markers compared with control group. p38 mitogen-activated protein kinase and nuclear factor-kappaB started to decrease a few hours after injury, whereas cyclooxygenase 2 and heat shock protein 47 expression decreased 7 and 14 days, respectively, after injury. Rosiglitazone also reduced neointima formation and inflammatory cell infiltration. In conclusion, rosiglitazone negatively regulated the inflammatory events involved in tissue repair at molecular and cellular levels. These results suggest that rosiglitazone plays a protective role in inflammatory vascular diseases.

Stimulatory Interactions between Human Coronary Smooth Muscle Cells and Dendritic Cells

“…Adhesion between DCs and VSMCs could be replicated in vivo upon carotid injury in the rat; this experimental animal model, as previously demonstrated by Rinaldi et al [23], is characterized by a significant inflammatory process. To the best of our knowledge, the present data are the first to demonstrate that DCs and CASMCs can stimulate each other by releasing soluble factors, hence they may cooperate in driving inflammation within the vascular wall, and that atorvastatin and rosiglitazone can interfere in such stimulation.…”

“…A positivity for IFNã was seen only in the positive control, but in none of the experimental cultures (data not shown). Given the anti-inflammatory properties of HMG-CoA reductase inhibitors [22] and of PPARγ agonists [23], their effect on cytokine release from co-cultures was measured: neither atorvastatin nor rosiglitazone influenced the release of cytokines in co-cultures (Fig. 1C).…”

“…In the present paper we could demonstrate that pre-treatment of CASMCs with atorvastatin (0.01–1 µmol/L) or rosiglitazone (1–20 µmol/L) significantly impairs the enhancement of mDC adhesion to CASMCs in response to inflammatory cytokines. Given the pleiotropic and anti-inflammatory effect of statins [22], [43]–[45] and PPARγ agonists [23], we assessed whether these drugs influenced also the release of cytokines in co-cultures. This did not happen, so the effect on cell adhesion may be a direct one.…”

Upregulation of Tanis mRNA Expression in the Liver is Associated with Insulin Resistance in Rats

“…Rosiglitazone treatment significantly reduced expression of inflammatory markers compared to control group. Rosiglitazone also reduced neointima formation and inflammatory cell infiltration (Rinaldi et al 2009). These results suggest that rosiglitazone plays a protective role in inflammatory vascular diseases.…”

“…They are widely used as insulin sensitizers for the treatment of type 2 diabetes. A recent study indicated that rosiglitazone negatively regulated the inflammatory events involved in tissue repair at molecular and cellular levels (Rinaldi et al 2009). Rosiglitazone treatment significantly reduced expression of inflammatory markers compared to control group.…”