OBJECTIVES: We sought to investigate whether the activation of the chemokine network observed in patients with coronary artery disease (CAD) could be modified by treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). BACKGROUND: Chemokines and chemokine receptors are important mediators in atherogenesis, and we hypothesized that the statins could affect the chemokine network in CAD. METHODS:Thirty CAD patients without previous statin therapy were randomized to receive atorvastatin (80 mg/day, n = 15) or simvastatin (20 mg/day, n = 15). Peripheral blood mononuclear cells (PBMCs) and plasma were obtained at baseline and after six months of statin therapy. Messenger ribonucleic acid (mRNA) expression of chemokines and chemokine receptors in PBMCs was analyzed by ribonuclease protection assay and real-time reverse-transcription polymerase chain reaction. Chemokines were also examined in the supernatants from unstimulated and lipopolysaccharide-stimulated PBMCs (and in plasma). RESULTS: Our main findings were: 1) gene expression of several chemokines (i.e., macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and interleukin [IL]-8) and chemokine receptors (i.e., CC chemokine receptor [CCR]1, CCR2, CCR4, and CCR5) was markedly increased among CAD patients compared with healthy control subjects; 2) treatment with atorvastatin and simvastatin markedly reduced the mRNA levels of some of these chemokines (i.e., MIP-1alpha, MIP-1beta, IL-8) and receptors (i.e., CCR1 and CCR2), with the most pronounced effect in the atorvastatin group; and 3) statin therapy reduced the spontaneous release of IL-8 and MIP-1alpha from PBMCs in CAD patients. CONCLUSIONS: This study demonstrates a down-regulatory effect of statins on the chemokine network in CAD patients, possibly contributing to the beneficial effects of statins in this disorder.
RCT Entities:
OBJECTIVES: We sought to investigate whether the activation of the chemokine network observed in patients with coronary artery disease (CAD) could be modified by treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). BACKGROUND: Chemokines and chemokine receptors are important mediators in atherogenesis, and we hypothesized that the statins could affect the chemokine network in CAD. METHODS: Thirty CAD patients without previous statin therapy were randomized to receive atorvastatin (80 mg/day, n = 15) or simvastatin (20 mg/day, n = 15). Peripheral blood mononuclear cells (PBMCs) and plasma were obtained at baseline and after six months of statin therapy. Messenger ribonucleic acid (mRNA) expression of chemokines and chemokine receptors in PBMCs was analyzed by ribonuclease protection assay and real-time reverse-transcription polymerase chain reaction. Chemokines were also examined in the supernatants from unstimulated and lipopolysaccharide-stimulated PBMCs (and in plasma). RESULTS: Our main findings were: 1) gene expression of several chemokines (i.e., macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and interleukin [IL]-8) and chemokine receptors (i.e., CC chemokine receptor [CCR]1, CCR2, CCR4, and CCR5) was markedly increased among CAD patients compared with healthy control subjects; 2) treatment with atorvastatin and simvastatin markedly reduced the mRNA levels of some of these chemokines (i.e., MIP-1alpha, MIP-1beta, IL-8) and receptors (i.e., CCR1 and CCR2), with the most pronounced effect in the atorvastatin group; and 3) statin therapy reduced the spontaneous release of IL-8 and MIP-1alpha from PBMCs in CAD patients. CONCLUSIONS: This study demonstrates a down-regulatory effect of statins on the chemokine network in CAD patients, possibly contributing to the beneficial effects of statins in this disorder.
Authors: Józef Dulak; Agnieszka Loboda; Agnieszka Jazwa; Anna Zagorska; Jacob Dörler; Hannes Alber; Wolfgang Dichtl; Franz Weidinger; Matthias Frick; Alicja Jozkowicz Journal: Endothelium Date: 2005 Sep-Dec
Authors: Hong-Hee Won; Suk Ran Kim; Oh Young Bang; Sang-Chol Lee; Wooseong Huh; Jae-Wook Ko; Hyung-Gun Kim; Howard L McLeod; Thomas M O'Connell; Jong-Won Kim; Soo-Youn Lee Journal: J Mol Med (Berl) Date: 2011-09-24 Impact factor: 4.599
Authors: Katarzyna Korybalska; Małgorzata Pyda; Stefan Grajek; Magdalena Lanocha; Andrzej Breborowicz; Janusz Witowski Journal: Clin Res Cardiol Date: 2010-02-07 Impact factor: 5.460
Authors: Cheuk-Man Yu; Qing Zhang; Linda Lam; Hong Lin; Shun-Ling Kong; Wilson Chan; Jeffrey Wing-Hong Fung; Kenny K K Cheng; Iris Hiu-Shuen Chan; Stephen Wai-Luen Lee; John E Sanderson; Christopher Wai-Kei Lam Journal: Heart Date: 2007-03-07 Impact factor: 5.994