ORIGINAL ARTICLE Higher circulating resistin protein and PBMCs resistin mRNA levels are associated with increased prevalence of small dense LDL particles in coronary artery disease patients Jelena Joksi  c,* Miron Sopi  c,* Vesna Spasojevi  c-Kalimanovska,* Tamara Gojkovi  c,* Aleksandra Zeljkovi  c,* Jelena Veki  c,* Kristina Andjelkovic, † Dimitra Kalimanovska-O stri  c †‡ and Zorana Jeli  c-Ivanovi  c* *Department of Medical Biochemistry, Faculty of Pharmacy, † Institute for Cardiovascular Diseases, Clinical Center of Serbia, and ‡ School of Medicine University of Belgrade, Belgrade, Serbia SUMMARY Recent in vitro experiments have indicated that human resis- tin increases the number of lipoprotein particles secreted by the human hepatocytes and also influences their quality, in terms of generating more proatherogenic lipid particles. The aim of this study is to investigate associations of plasma resistin and peripheral blood mononuclear cells (PBMCs) resistin mes- senger RNA (mRNA) levels with different prevalence of small, dense low-density lipoprotein particles (sdLDL) in patients with indications for coronary angiography. This study included 65 patients requiring coronary angiography. There were 41 patients without significant stenosis and 24 patients with signif- icant stenosis in at least one major coronary artery. Circulating resistin was measured by enzyme-linked immunosorbent assay; PBMC resistin mRNA was determined by real-time poly- merase chain reaction. The LDL and high density lipoprotein subclasses were determined by gradient gel electrophoresis. Plasma resistin (P = 0.031) and PBMCs resistin mRNA (P = 0.004) were significantly higher in patients with propor- tion of sdLDL particles ≥ 50%, compared to the group with relative proportion of sdLDL particles < 50%. Plasma resistin correlated positively with creatinine (r = 0.456, P < 0.001) and resistin mRNA (r = 0.298, P = 0.014) but negatively with body mass index (r = 0.254, P = 0.034) and total cholesterol (r = 0.286, P = 0.021). Multiple linear regression analysis revealed LDL particle diameter as the only independent predictor of resistin mRNA (R 2 = 0.258; adjR 2 = 0.190). A sig- nificant association between resistin, both PBMCs mRNA and plasma protein, and the relative proportion of sdLDL particles in the circulation of coronary artery disease patients has been established, which implies that increased gene expression of resistin in PBMCs and higher resistin concentration in plasma are related to pro-atherogenic LDL particle phenotype. Key words: coronary artery disease, gene expression, human, resistin, small dense LDL. INTRODUCTION Coronary artery disease (CAD) remains one of the major causes of morbidity and loss of quality of life in the industri- alized world. The pathogenesis of CAD lays in the develop- ment of dyslipidemia, increased proinflammatory processes and consequently atherosclerosis evolvement and progression. 1 One of the major risk factors for CAD is elevated concentration of low density lipoprotein cholesterol (LDL-C). However, numer- ous studies have demonstrated that the quality of LDL parti- cles, rather than simply the levels of LDL-C, exerts a potent influence on cardiovascular disease (CVD) risk. 2,3 Namely, LDL consists of a heterogeneous spectrum of particles, which are different in size, density and protein/lipid content, with highly variable atherogenic potential. It has been firmly estab- lished that small dense LDL (sdLDL) particles are highly atherogenic and particularly contribute to the development of CVD. 2–4 Human resistin, a 12.5 kDa peptide, belongs to a family of cysteine-rich secretory proteins that includes resistin-like mole- cules. 5 Unlike in mice, where it is expressed predominately by adipocytes and has been linked to insulin resistance and type 2 diabetes development, 6 human resistin is a potent proinflamma- tory cytokine, which is expressed and secreted mainly by periph- eral blood mononuclear cells (PBMCs), macrophages and bone marrow cells. 7 In vitro experiments have shown that human resis- tin exerts many effects contributing to atherosclerosis: resistin leads to decreased expression of nitric oxide synthase in human coronary artery endothelial cell lines (HCAECL); 7 increases monolayer permeability of HCAECLs; 8 accelerates plaque pro- gression by stimulating monocyte infiltration, 9 up-regulates endothelin-1, vascular cell adhesion molecule-1, intracellular adhesion molecule-1 and monocyte chemoattractant protein in vascular endothelial cells; 7 and increases lipid accumulation in macrophages contributing to foam cell formation. 7,10 In vivo, Correspondence: Jelena Joksi  c, VojvodeStepe 450, Department of Med- ical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia. Email: jelenaj@pharamcy.bg.ac.rs Received 30 July 2015; revision 8 October 2015; accepted 9 October 2015. © 2015 Wiley Publishing Asia Pty Ltd Clinical and Experimental Pharmacology and Physiology (2016) 43, 22–28 doi: 10.1111/1440-1681.12503