title: 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.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Araújo
authors.forename: Monaliza A
authors.initials: MA
authors.lastname: Rocha
authors.forename: Mônica And
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Paula P
authors.initials: PP
authors.lastname: Campos
authors.forename: Luciano S A
authors.initials: LS
authors.lastname: Capettini
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Lemos
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Andrade
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006454:Hemoglobins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020007:Implants, Experimental; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010537:Peritoneum / Q000098:blood supply; D010538:Peritonitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011140:Polyurethanes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005229:Fatty Acids, Monounsaturated; D006454:Hemoglobins; D007211:Indoles; D011140:Polyurethanes; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C115016:polyetherurethane; D009569:Nitric Oxide; D000077340:Fluvastatin; D009195:Peroxidase; D000118:Acetylglucosaminidase