Pleiotropic effects of pitavastatin: a pilot study using the saphenous vein endothelial cell model of endothelial injury and prevention of atherosclerosis.

OBJECTIVE: Cardiovascular diseases are responsible for the majority of deaths on a global scale. Atherosclerosis is the main risk factor for cardiovascular disorders and represents a complex phenomenon associated with endothelial dysfunction and inflammation. Statins, especially atorvastatin (ATV) and pitavastatin (PTV), are common agents used to control ongoing atherosclerotic events in the body to minimize cardiovascular disease-based deaths. MATERIALS AND METHODS: The present study aimed at comparing the efficacy of ATV and PTV in a cell line model of inflammation. Human saphenous vein cells were treated with TNF-alpha to mimic atherosclerotic conditions, and the cells were divided into 7 groups, including control, DMSO, TNF-alpha (10 ng/mL-6 hours), ATV (50 µM/24 hours), PTV (2 µM/24 hours), ATV (50 µM/24 hours)+TNF-alpha (10 ng/mL-6 hours) and PTV (2 µM/24 hours)+TNF-alpha (10 ng/mL-6 hours). The expression levels of 20 proinflammatory cytokines and chemokines were investigated in these groups using a human atherosclerosis antibody array. RESULTS: Possible pathway interactions were determined by STRING and PANTHER analyses. Comparison with the effect of ATV indicated that PTV reduced the levels of 4 proinflammatory cytokines: CCL11, CSF2, CCL20, and TGFB1 (p<0.05). CONCLUSIONS: Pleiotropic effects of pitavastatin against cardiovascular diseases appeared to be better; however, additional studies are required to compare statins and to identify new drugs that maintain broader protection from the risks of cardiovascular diseases.

The Correlation of Increased CRP Levels with NFKB1 and TLR2 Polymorphisms in the Case of Morbid Obesity.

Morbid obesity (MO) is associated with an increase in circulating levels of systemic acute phase proteins such as C-reactive protein (CRP). Toll-like receptor is possible candidate for inflammatory responses which is mainly mediated by NFKB1. The aim of this study was to investigate the relationship between NFKB1 and Toll-like receptor (TLR) 2 polymorphisms and the risk of MO in a Turkish population in the context of CRP serum levels which may contribute to susceptibility to the disease. We analysed the distribution of NFKB1-94 ins/del ATTG rs28362491 and TLR2 Arg753Gln rs5743708 polymorphisms using PCR-RFLP method and CRP serum levels using ELISA method in 213 MO and 200 healthy controls. The frequency of the ins/ins genotype and ins allele of rs28362491 was significantly higher in the patients compared to control group (P: 0.0309; P: 0.0421, respectively). Additionally, the frequency of GG genotype and G allele of rs5743708 was found to be statistically higher in the patient group (P: 0.0421; P < 0.0001, respectively). In addition, serum CRP levels (>20 mg/l) in MO patients with ins/ins genotype were significantly higher than in patients with del/ins genotype (P: 0.0309). Serum CRP levels were also higher in MO patients with GG genotype and G allele (P: 0.0001). According to combined analysis, the wild type of rs28362491 and rs5743708 polymorphisms (ins/ins/GG genotype) was also significantly higher in the patient group versus the control group when compared with the combined ins/ins/GA and del/ins/GA genotype (P < 0.0001). Therefore, our findings suggest that rs28362491 and rs5743708 polymorphisms were significantly associated with MO disease through acting by modulating serum CRP levels.

Association of NFKB1 and NFKBIA polymorphisms in relation to susceptibility of Behçet's disease.

Behçet's disease (BD) is a chronic inflammatory autoimmune disease. Although raised levels of proinflammatory cytokines in BD have been reported, the pathogenesis is still unknown. The aim of this study was to investigate the association of NFKB1 and NFKBIA polymorphisms and their single and combined analysis effects on susceptibility of BD in Turkish population. We analysed the distribution of NFKB1 -94 ins/del ATTG (rs28362491) and NFKBIA 3' UTR A→G (rs696) polymorphisms using PCR-RFLP method in 89 patients with BD and 190 controls in this population. Statistical analysis of the results was performed by calculating OR, and 95% CI via χ(2) test and using Bonferroni correction. According to the significant results of both single and combined genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were significantly higher in patients with BD (Pc = 0.003, 0.004, respectively). Also, higher frequencies of the rs696 variant containing AA genotype was found in patients with BD (Pc = 0.0033), whereas no statistical significant differences in distribution of the alleles of rs696 polymorphism in patients and controls. In addition, according to the combined genotype analysis, the wild type of both rs28362491 and rs696 polymorphisms (ins/ins/AA genotype) was also significantly higher in BD cases (Pc = 0.044). Our findings prove that both single and combined genotype analysis of rs28362491 and rs696 polymorphisms indicate that the wild genotypes of both two SNPs (ins/ins and AA genotypes) and ins/ins/AA combined genotype are strongly associated with enhanced risk of BD in a Turkish population.