Implant‐induced intraperitoneal inflammatory angiogenesis is attenuated by fluvastatin

Clinical and Experimental Pharmacology and Physiology - Tập 38 Số 4 - Trang 262-268 - 2011
Fernanda de Assis Araújo1, M.A. Rocha2, Mônica AND Ferreira2, Paula Peixoto Campos2, Luciano dos Santos Aggum Capettini2, Virgı́nia S. Lemos2, Sílvia Passos Andrade2
1Department of Physiology and Biophysics, Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
2Department of Physiology and Biophysics and Department of General Pathology, Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil

Tóm tắt

Summary1. 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.

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Clinical and Experimental Pharmacology and Physiology

Tập 38 Số 4

262-268

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