Pharmacological evidence for the involvement of the opioid system in the antidepressant-like effect of simvastatin in mice: Without tolerance and withdrawal syndrome.

Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, have been shown to be effective in reducing depression in animal models. The present study aimed to investigate the potential antidepressant-like activity of simvastatin and the possible involvement of opioid systems in the mouse forced swimming test (FST). After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of depressive behavior in mice. Simvastatin (20, 30, and 40 mg/kg, i.p.) or morphine (0.01, 0.1, 1 and 10 mg/kg, i.p.) were administrated 30 min before the OFT or FST. Results showed that simvastatin produced antidepressant effect in a dose-dependent manner. The effect of simvastatin (30 mg/kg) was prevented by the pre-treatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). In addition, a sub-effective dose of simvastatin (20 mg/kg) produced a synergistic antidepressant-like effect in the FST with a sub-effective dose of morphine (0.1 mg/kg) that it was reversed by naloxone. Moreover, in contrast to morphine, treatment with simvastatin for six days induced neither tolerance to the antidepressant-like effect nor withdrawal signs. In conclusion, these findings demonstrated that simvastatin elicited antidepressant-like action possibly through the stimulation of opioidergic pathways, without inducing tolerance and withdrawal signs.

Cancer biomarkers in atherosclerotic plaque: Evidenced from structural and proteomic analyses.

Atherosclerosis and cancer are the leading causes of mortality around the world that share common pathogenic pathways. The aim of this study is the investigation of the protein profile of atherosclerotic plaque in order to find similar biomarker between cancer and atherosclerosis. The small pieces of human coronary artery containing advanced atherosclerotic plaque is obtained from patients during bypass surgery. Structural characterization of type V plaque, including fibrous connective tissue, necrotic lipid core, cholesterol clefts and calcium deposits are performed using high resolution transmission electron microscopy (HR-TEM). The protein profile of atherosclerosis plaque is also analyzed using 2-dimensional electrophoresis and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF). TEM analysis shows that vascular smooth muscle cells (VSMCs) exhibit different and uncommon morphologies in atherosclerotic plaque which is correlated to the proliferative state of the cells. The proteomics analysis reveals proteins related to atherosclerosis formation including Mimecan, Ras Suppressor Protein-1 (RSUP-1) and Cathepsin D which identified as biomarker of cancerous tumors. The expression of Mimecan and RSUP-1 is down-regulated in atherosclerotic plaque while the expression of Cathepsin D is up-regulated. These data support that atherosclerotic plaque presents some degree of tumorgenesis with the significant activity of VSMCs as the key player in atherogenesis.

Association between rs10757274 and rs2383206 SNPs as Genetic Risk Factors in Iranian Patients with Coronary Artery Disease.

Background: There are only a few reports concerning the genetic risk factors for coronary artery disease (CAD). However, 2 polymorphisms of rs10757274 and rs2383206 on chromosome 9p21.3 have been shown recently to be associated with CAD in certain populations. This is the 1st study to investigate their validity and association with CAD in a sample of the Iranian population. Methods: Genomic DNA was extracted from the peripheral blood of all participants, consisting of 111 cases with CAD and 100 normal controls with normal coronary angiographies. Genotyping of rs10757274 and rs2383206 was performed in the cases and controls using designed mismatch primers via the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Statistical analysis presented a significant association between the rs10757274 GG (p value = 0.029, χ2 = 7.078) and rs2383206 GG (p value = 0.036, χ2 =6.658) genotypes and CAD among the cases as compared with the normal controls. Haplotype analysis of rs10757274 and rs2383206 polymorphisms showed 43% GG/GG haplotype with a significant association with CAD (p value = 0.014, χ² = 6.058). Conclusion: The results of this study provide an insight into the underlying molecular mechanism of CAD pathogenesis and pave the way for future functional studies on these variants.