Differential expression of cytokines, chemokines and chemokine receptors in patients with coronary artery disease Rômulo Tadeu Dias de Oliveira a , Ronei Luciano Mamoni a , José Roberto Matos Souza b , Juliano Lara Fernandes b , Francisco José O. Rios c , Magnus Gidlund c , Otávio Rizzi Coelho b , Maria Heloisa Souza Lima Blotta a, ⁎ a Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil b Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil c Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil Received 31 October 2007; received in revised form 15 February 2008; accepted 4 April 2008 Available online 9 July 2008 Abstract Monocytes/macrophages and lymphocytes have a key role in the pathogenesis of atherosclerosis through the production of inflammatory and anti-inflammatory cytokines. We evaluated mRNA expression and protein production of CCL2, CXCL8, CXCL9, CXCL10, IFN-γ and IL-10 in vitro as well as the expression of the CCR2 and CXCR3 receptors in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy controls in the presence or absence of oxidized LDL (oxLDL). Patients with CAD showed higher constitutive expression of CCL2, CXCL8, CXCL9, CXCL10 and IFN-γ mRNA and, after stimulation with oxLDL, higher expression of CCL2 and CXCL8 mRNA than the control group. We also detected higher levels of CCL2 and CXCL8 in supernatants of oxLDL-stimulated PBMCs from CAD patients than in corresponding supernatants from controls. Patients with CAD had a higher percentage of constitutive CCR2 + and CXCR3 + cells after stimulation with oxLDL. Among CAD patients, the main differences between the stable (SA) and unstable angina (UA) groups were lower IL-10 mRNA production in the latter group. Altogether, our data suggest that PBMCs from CAD patients are able to produce higher concentrations of chemokines and cytokines involved in the regulation of monocyte and lymphocyte migration and retention in atherosclerotic lesions. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Atherosclerosis; Inflammation; Chemokines; Coronary artery disease; Angina 1. Introduction Chronic inflammation is an important determinant of atherosclerosis, and a number of inflammatory mediators such as adhesion molecules, cytokines and chemokines are involved in the initiation and progression of atherosclerotic lesions [1]. Recruitment of circulating mononuclear leuko- cytes is one of the earliest events in atherosclerosis, and chemokines play an important role promoting the migration and activation of these cells at the site of inflammation [2]. Monocyte chemoattractant protein-1 CCL2 (MCP-1), a member of the CC chemokines, is involved in the initiation and development of atherosclerotic lesions, where it acts as a specific chemotactic factor for monocytes/macrophages, with its effects being exerted mainly through the CC chemokine receptor 2 (CCR2) [3]. A considerable number of studies have shown that CCL2 (mRNA and protein) is present in human atherosclerotic lesions [4], and that the formation of these lesions in mice lacking CCR2 or CCL2 is greatly re- duced [5,6]. Interleukin-8 (CXCL8/IL-8), an ELR CXC International Journal of Cardiology 136 (2009) 17 – 26 www.elsevier.com/locate/ijcard ⁎ Corresponding author. Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), PO Box 6111, 13083-970, Campinas, SP, Brazil. Tel.: +55 19 3521 9453; fax: +55 19 3521 9434. E-mail address: heblotta@fcm.unicamp.br (M.H.S.L. Blotta). 0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.04.009