Short Communication The dual behavior of heat shock protein 70 and asymmetric dimethylarginine in relation to serum CRP levels in type 2 diabetes Manouchehr Nakhjavani a, ⁎, Afsaneh Morteza a , Firuzeh Asgarani a , Omid Khalilzadeh a , Zaniar Ghazizadeh a , Seyede Zahra Bathaie b , Alireza Esteghamati a a Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran b Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran abstract article info Article history: Accepted 30 January 2012 Available online 13 February 2012 Keywords: HSP70 Heat-shock proteins N,N-dimethylarginine (asymmetric dimethylarginine) C-reactive protein Type 2 diabetes mellitus Background: Experimental evidence suggests that heat shock proteins (HSP) and asymmetric dimethylargi- nine (ADMA) are induced in the state of chronic inflammation and stress conditions. They are both inhibitors of nitric oxide synthase (NOS). The aim of this study was to evaluate the correlation between ADMA and HSP70, in patients with type 2 diabetes with respect to serum levels of C reactive protein (CRP). Methods: We quantified serum HSP70, ADMA and CRP in 80 newly-diagnosed patients with type 2 diabetes plus 80 age-, sex and BMI-matched healthy controls. The patients and controls were also stratified into groups of high and low CRP levels (cut-point: 2.5 mg/ml). Results: Patients with type 2 diabetes had significantly higher serum HSP70 (0.52 [0.51–0.66] vs. 0.27 [0.26– 0.36], p b 0.001), ADMA (0.86 [0.81–0.92] vs. 0.72 [0.71–0.85], p b 0.05) and CRP (2.9 [1.7–3.4] vs. 1.6[1.2–2.3], p b 0.05) compared with healthy controls. Serum HSP70 and ADMA levels were significantly correlated in pa- tients with high CRP levels (r = 0.89, p b 0.01), whereas there were no correlation in patients with low CRP (r=-0.37, p = 0.07) and controls. This correlation was significant (r = 0.77, p b 0.001) in patients with high CRP and also in patients with low CRP levels (r =-0.51, p b 0.05), after multiple adjustments for LDL and HDL levels. Discussion: We showed that, in a state of high inflammation; serum levels of ADMA parallel the HSP70 levels. However in low inflammation, they are negatively correlated. The duality in HSP70 and ADMA correlation may be related to the duality of NOS function in low and high CRP levels. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Inflammation is a pathological process characterized by injury or destruction of the tissue caused by a variety of cytological and chem- ical reactions (Cullen et al., 2003). Most inflammatory reactions can be clinically detected by pain and swelling. However, inflammation at the molecular level may not be initially detected. This will usually happen in the atherosclerosis, coronary heart disease, type 2 diabetes and metabolic syndrome (Cullen et al., 2003; Dandona et al., 2005). Some years ago a hypothesis was proposed suggesting that elements of innate immune system, such as acute phase reactants and C reac- tive proteins (CRP) contribute to the development of type 2 diabetes (Crook, 2004; Dandona et al., 2005). Later on, this idea was supported by studies reporting elevated levels of inflammatory markers includ- ing white blood cell count, CRP, asymmetric dimethylarginine (ADMA) and heat shock proteins (HSP) in patients with type 2 diabe- tes (Nakhjavani et al., 2010a, 2010b, 2011). Heat-shock proteins (HSP) or stress proteins are molecular chap- erones that play an important role in protein folding, intracellular transport of proteins, and coping with proteins denatured by heat and other stressors (Ritossa, 1996). Heat-shock proteins are named according to their molecular weight (HSP70: 70 kDa in size), are highly conserved and present in all cells of all organisms (Li and Srivastava, 2004). HSPs, play crucial roles in folding/unfolding of pro- teins, assembly of multiprotein complexes, transport/sorting of pro- teins into correct subcellular compartments, cell-cycle control and signaling, and protection of cells against stress/apoptosis (Li and Srivastava, 2004; Santoro, 2000). Production of high levels of heat shock proteins can be triggered by exposure to environmental stressors Gene 498 (2012) 107–111 Abbreviations: HSP, heat shock protein; HSP70, heat shock protein 70; ADMA, asymmetric dimethylarginine; NO, nitric oxide; NOS, nitric oxide synthase; nNOS, brain constitutive NOS; eNOS, endothelial constitutive NOS; iNOS, inducible constitu- tive NOS; CRP, C reactive protein; FPG, fasting plasma glucose; TG, triglycerides; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein- cholesterol; CV, coefficient of variants; HOMA-IR, homeostatic model assessment of insulin resistance; BMI, body mass index. ⁎ Corresponding author at: Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, P.O. Box 13145-784, Iran. Tel.: +98 21 8841791; fax: +98 21 64432466. E-mail addresses: nakhjavanim@tums.ac.ir (M. Nakhjavani), aafsaneh03@gmail.com (A. Morteza), fasgarani@tums.ac.ir (F. Asgarani), o.khalilzadeh@gmail.com (O. Khalilzadeh), xaniar@gmail.com (Z. Ghazizadeh), bathai_z@modares.ac.ir (S.Z. Bathaie), esteghamati@tums.ac.ir (A. Esteghamati). 0378-1119/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.gene.2012.01.085 Contents lists available at SciVerse ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene