3‐Hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor (fluvastatin) decreases inflammatory angiogenesis in mice

APMIS - Tập 121 Số 5 - Trang 422-430 - 2013
Fernanda de Assis Araújo1, M.A. Rocha1, Luciano dos Santos Aggum Capettini1, Paula Peixoto Campos1, Mônica Alves Neves Diniz Ferreira2, Virgı́nia S. Lemos1, Sílvia Passos Andrade1
1Departments of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
2Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil

Tóm tắt

Statins, 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors, have been shown to ameliorate a number of vascular diseases. We evaluated the inflammatory and angiogenic components of the fibrovascular tissue induced by subcutaneous implants in mice and their modulation by fluvastatin. Our results showed that the statin (0.6 and 6 mg/kg/day) inhibited hemoglobin (Hb) content (51%) and vascular endothelial growth factor (VEGF) levels (71%) in the treated group compared with the control group. The inflammatory component, as assessed by N‐acetyl‐β‐D‐glucosaminidase activity and tumor necrosis factor‐α (TNF‐α) level was also decreased by the compound. In the treated group; the inhibition of the enzyme activity was 33% and the cytokine was 67% relative to the control. In these implants the statin was also able to decrease nitric oxide (NO) production, detected with an NO‐sensitive electrode. To our knowledge this is the first study demonstrating an inhibitory role of fluvastatin on the production of NO in inflammatory angiogenesis of newly formed fibrovascular tissue.

Từ khóa


Tài liệu tham khảo

Bobik A, 1993, Vascular derived growth factors: cell biology, pathophysiology, and pharmacology, Pharmacol Rev, 45, 1

10.1161/01.CIR.0000129500.29229.92

10.1016/S0014-5793(01)02337-7

10.1097/01.cad.0000131680.83518.91

10.1161/01.ATV.0000012283.15789.67

10.1016/j.biopha.2009.03.003

10.1161/hh2201.100319

10.1038/79510

10.1161/01.RES.0000014081.30867.F8

10.1161/01.RES.0000028149.15986.4C

10.1111/j.1600-0463.2008.01148.x

10.1111/j.1476-5381.1992.tb13412.x

10.1002/path.1711710412

10.1055/s-2008-1039107

10.1161/hc0602.103393

10.1111/j.1440-1681.2011.05496.x

10.1186/1423-0127-17-45

10.1161/01.HYP.36.6.923

10.1016/S0195-668X(02)00419-0

10.1097/00043798-200306000-00004

10.1161/01.HYP.0000053552.86367.12

10.1016/S0741-5214(03)00555-X

10.1161/01.CIR.0000093190.53478.78

10.1016/S1054-3589(08)60274-4

10.1161/01.ATV.17.8.1521

10.1038/labinvest.3780115

10.1016/j.cccn.2004.10.007

10.1158/0008-5472.CAN-08-3076

10.1111/j.1365-2222.2009.03334.x

10.1161/hc0402.104119

10.1016/j.atherosclerosis.2003.11.004

10.1073/pnas.0401996101

10.1007/BF02256431

10.1007/s002109900150

10.1074/jbc.272.50.31725

10.1172/JCI119736

10.1016/S0165-6147(00)01499-1

10.1002/eji.201141674

Thông tin
Thông tin xuất bản

APMIS

Tập 121 Số 5

422-430

Thông tin tác giả