Implant‐induced intraperitoneal inflammatory angiogenesis is attenuated by fluvastatin

Abstract

1. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitors, exert anti-inflammatory, anti-oxidant and anti-angiogenic effects. These effects are associated with downregulation of pro-inflammatory/pro-angiogenic molecules and upregulation of endothelial nitric oxide synthase (e-NOS) expression/nitric oxide (NO) production. 2. Using the murine sponge model to induce chronic intraperitoneal inflammatory response, we evaluated the inflammatory components, angiogenic and NO production of the fibrovascular tissue, and their modulation by fluvastatin. 3. Our results showed that fluvastatin (0.6 and 6 mg/kg per day) inhibited haemoglobin (Hb) content 4.9±0.4 (n=15; control) vs 2.2±0.2 (n=6; fluvastatin 0.6) and 1.8±0.2 (n=6; fluvastatin 6.0) and the number of vessels in the treated group when compared with the control group. The inflammatory component, as assessed by myeloperoxidase and N-acetyl-β-d-glucosaminidase activities and by the pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α) and Monocyte chemotactic protein-1 (MCP-1)/CCL2/JE levels, was also decreased by the compound. In the treated group, inhibition of both enzyme activities was 54% and 57%, respectively. The levels of the cytokines (TNF-α and CCL2/JE) intra-implant were decreased relative to the control. In these implants, fluvastatin was also able to increase NO production, as detected with an NO-sensitive electrode. 4. The inhibitory function of fluvastatin on key components of intraperitoneal inflammatory angiogenesis shown in the present study is clearly associated with the modulatory effects of this statin on vascular endothelial growth factor, TNF-α and NO production.

Nanotube Action between Human Mesothelial Cells Reveals Novel Aspects of Inflammatory Responses

“…therapeutic sanctions, such as the application of statins, which may have to be precisely adopted to the individual patient background, in order to 1) induce potential beneficial effects and 2) not to provoke undesired reverse effects. In support of this notion it was shown, that statin treatment can be associated with improved survival [21]–[24] and anti-inflammatory effects in peritoneal dialysis patients [25], [26]. Such potential interrelations will now have to be approached in great detail, whereby several problems, e.g.…”

Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in intraperitoneal implant in mice

“…The intraperitoneal implants were shown to be firmly adhered to surrounding organs (liver and/or intestines), highly vascularized, infiltrated with inflammatory cells, and producing pro-inflammatory and pro-angiogenic cytokines [9,10]. …”

“…We have recently reported that implantation of a synthetic matrix in the peritoneal cavity in mice induced a fibroproliferative process whose components, inflammatory cell recruitment, angiogenesis, and extracellular matrix deposition were identified and modulated by various compounds [9,10]. We hypothesized that propolis might be of potential therapeutic value in modulating the components of these lesions in our model.…”

Foreign Body Response to Subcutaneous Implants in Diabetic Rats

“…This method has been modified and used to determine angiogenesis in various experimental models and tissues, including the sponge implant model [6], [12]–[13]. All implants were individually homogenized (Tekmar TR-10, Cincinnati, OH) in 5 mL of Drabkin reagent (Labtest, São Paulo, Brazil) and centrifuged at 12.000 rpm for 20 min.…”