gw9662 and Hypercholesterolemia

gw9662 has been researched along with Hypercholesterolemia* in 1 studies

Other Studies

1 other study(ies) available for gw9662 and Hypercholesterolemia

Article	Year
HMG-CoA reductase inhibition reduces monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated monocyte recruitment in vivo. Circulation, 2005, Mar-22, Volume: 111, Issue:11 The migration of circulating monocytes to the arterial wall during atherogenesis is largely modulated by activation of the CC chemokine receptor 2 (CCR2), a dominant monocyte chemotaxis receptor. The present study investigated whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition affects CCR2 gene expression and CCR2-dependent monocyte recruitment.. Competitive reverse transcription-polymerase chain reaction analysis and flow cytometry showed that simvastatin, an HMG-CoA reductase inhibitor, dose-dependently reduced monocyte CCR2 mRNA and protein expression. Treatment of 21 normocholesterolemic men with simvastatin (20 mg/d for 2 weeks) decreased CCR2 protein and mRNA expression in circulating monocytes. Promoter and electrophoretic mobility shift assays showed that simvastatin activated a peroxisome proliferator response element in THP-1 monocytes. Moreover, simvastatin-induced CCR2 downregulation was completely reversed by the synthetic peroxisome proliferator-activated receptor-gamma antagonist GW9662. Simvastatin-treated monocytes showed little chemotaxis movement in response to monocyte chemoattractant protein-1 (MCP-1), a specific CCR2 ligand. Treatment of C57/BL6 mice with simvastatin (0.2 microg/g body weight IP, daily for 1 week) inhibited transmigration of CD80+ monocytes to the MCP-1-injected intraperitoneal space. Moreover, few circulating inflammatory cells from simvastatin-treated Sprague-Dawley rats (0.2 microg/g body weight IP, daily for 2 weeks) were recruited to the aortic wall of hypercholesterolemic littermates.. The inhibition of CCR2/MCP-1-dependent monocyte recruitment by simvastatin may prevent excessive accumulation of monocytes in the arterial wall during atherogenesis. Topics: Anilides; Animals; Aorta; Cells, Cultured; Chemokine CCL2; Chemotaxis, Leukocyte; Depression, Chemical; Diet, Atherogenic; Down-Regulation; Drug Evaluation, Preclinical; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Mevalonic Acid; Mice; Mice, Inbred C57BL; Monocytes; Polyisoprenyl Phosphates; PPAR gamma; Rats; Rats, Sprague-Dawley; Receptors, CCR2; Receptors, Chemokine; RNA, Messenger; Rosiglitazone; Sesquiterpenes; Simvastatin; Thiazolidinediones	2005

Article

Year

HMG-CoA reductase inhibition reduces monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated monocyte recruitment in vivo.

Circulation, 2005, Mar-22, Volume: 111, Issue:11

The migration of circulating monocytes to the arterial wall during atherogenesis is largely modulated by activation of the CC chemokine receptor 2 (CCR2), a dominant monocyte chemotaxis receptor. The present study investigated whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition affects CCR2 gene expression and CCR2-dependent monocyte recruitment.. Competitive reverse transcription-polymerase chain reaction analysis and flow cytometry showed that simvastatin, an HMG-CoA reductase inhibitor, dose-dependently reduced monocyte CCR2 mRNA and protein expression. Treatment of 21 normocholesterolemic men with simvastatin (20 mg/d for 2 weeks) decreased CCR2 protein and mRNA expression in circulating monocytes. Promoter and electrophoretic mobility shift assays showed that simvastatin activated a peroxisome proliferator response element in THP-1 monocytes. Moreover, simvastatin-induced CCR2 downregulation was completely reversed by the synthetic peroxisome proliferator-activated receptor-gamma antagonist GW9662. Simvastatin-treated monocytes showed little chemotaxis movement in response to monocyte chemoattractant protein-1 (MCP-1), a specific CCR2 ligand. Treatment of C57/BL6 mice with simvastatin (0.2 microg/g body weight IP, daily for 1 week) inhibited transmigration of CD80+ monocytes to the MCP-1-injected intraperitoneal space. Moreover, few circulating inflammatory cells from simvastatin-treated Sprague-Dawley rats (0.2 microg/g body weight IP, daily for 2 weeks) were recruited to the aortic wall of hypercholesterolemic littermates.. The inhibition of CCR2/MCP-1-dependent monocyte recruitment by simvastatin may prevent excessive accumulation of monocytes in the arterial wall during atherogenesis.

Topics: Anilides; Animals; Aorta; Cells, Cultured; Chemokine CCL2; Chemotaxis, Leukocyte; Depression, Chemical; Diet, Atherogenic; Down-Regulation; Drug Evaluation, Preclinical; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Mevalonic Acid; Mice; Mice, Inbred C57BL; Monocytes; Polyisoprenyl Phosphates; PPAR gamma; Rats; Rats, Sprague-Dawley; Receptors, CCR2; Receptors, Chemokine; RNA, Messenger; Rosiglitazone; Sesquiterpenes; Simvastatin; Thiazolidinediones

2005