Contribution of Interleukin-6 system genes polymorphisms to the development of coronary atherosclerosis.

Coronary artery disease (CAD) continues to be a main cause of high cardiovascular morbidity and mortality and its prevalence is expected to increase as the population ages, so its prevention is a key public health policy goal. The risk of developing atherosclerosis is related to a complex interaction of genetic, environmental and lifestyle factors. Significant progress has been made in understanding the genetic architecture of this disease in the last decade. In this article, we attempt to map the current knowledge about the genetics of atherosclerosis, in particular the interleukin-6 system and its contribution to the development of coronary atherosclerosis.

The association of PLA2G2A single nucleotide polymorphisms with type IIa secretory phospholipase A2 level but not its activity in patients with stable coronary heart disease.

BACKGROUND: Single nucleotide polymorphisms (SNPs) of the secretory phospholipase A2 type IIa (sPLA-IIa) gene (PLA2G2A) affect sPLA2-IIa level and activity in patients with diabetes mellitus, acute coronary syndrome or recent cardiovascular surgical interventions. Our study examined the effects of PLA2G2A SNPs on sPLA2-IIa levels and activity in patients with stable CHD. METHODS AND RESULTS: The study included a total of 396 patients (30% women). Six SNPs of PLA2G2A: rs1774131, rs11573156, rs3753827, rs2236771, rs876018, and rs3767221, sPLA2-IIa level and activity were determined for all patients. Four SNPs (rs1774131, rs11573156, rs3753827, rs3767221) correlated with sPLA2-IIa level but not activity with the strongest correlation observed for rs11573156 (r=0.49, p=3.7·10(-13)). All partial correlations controlling for rs11573156 became insignificant, whereas, the partial correlation of rs11573156 with sPLA2-IIa level controlling for other SNPs remained significant. Only rs11573156 showed association with sPLA2-IIa level in multiple regression analysis. Haplotype CGGGTT was associated with a significantly higher sPLA2-IIa level but not activity compared with all other haplotypes after adjustment for gender, age, diabetes mellitus and statin use (p=0.0023). CONCLUSIONS: According to our results the examined SNPs affect the sPLA2-IIa level to a greater extent than its activity in patients with stable CHD. It seems that, the impact of these SNPs on sPLA2-IIa level is caused by their linkage to rs11573156 whose minor alleles were associated with higher sPLA2-IIa level. At the same time haplotype CGGGTT, which includes the minor allele of rs11573156, was the dominant haplotype and was associated with the highest sPLA2-IIa level.

Two-year follow-up of percutaneous coronary intervention using EucaTax or Cypher.

BACKGROUND: The EucaTax stent (EUPES) is a coronary stent with biodegradable polymer and camouflage coating that has been developed to promote the complete elution of drugs and decrease the risk of late complications. The aim of this study was to evaluate the efficacy and safety of the double-coated EUPES in patients with stable angina versus sirolimus-eluting stent CYPHER (SES) with permanent polymer coating. METHODS AND MATERIALS: The study included consecutive patient with at least 70% de novo coronary lesions in one or two native coronary arteries and who had undergone the coronary stenting using either EUPES or SES. We evaluated the 2-year major adverse cardiac events (MACE) rates, including total death (cardiac, non-cardiac), myocardial infarction (MI), target lesion revascularisation (TLR) and stent thrombosis. RESULTS: Between 2006 and 2009 this observational, prospective, single centre study included 602 patients (282 with EUPES and 320 with SES). At 2years, the rates of TLR (16.3% versus 6.25%; p=0.0001) and MACE (18.4% versus 7.8%; p=0.001) were significantly higher in the EUPES than in the SES group. The rate of TLR was significantly higher in the EUPES group compared with SES group in stenting of artery with a diameter less than 3mm, using stent length more than 18mm, as well as when the residual stenosis was more than 12%. CONCLUSIONS: We found that EUPES was inferior to SES during the 2-year follow-up with respect to rates of MACE and TLR that were significantly higher in the EUPES than in the SES group.

Antioxidants decreases the intensification of low density lipoprotein in vivo peroxidation during therapy with statins.

The oxidative modification of low density lipoprotein (LDL) is thought to play an important role in atherogenesis. Drugs of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) family are usually used as a very effective lipid-lowering preparations but they simultaneously block biosynthesis of both cholesterol and ubiquinone Q10 (coenzyme Q), which is an intermediate electron carrier in the mitochondrial respiratory chain. It is known that reduced form of ubiquinone Q10 acts in the human LDL as very effective natural antioxidant. Daily per os administration of HMG-CoA reductase inhibitor simvastatin to rats for 30 day had no effect on high-energy phosphates (adenosin triphosphate, creatine phosphate) content in liver but decreased a level of these substances in myocardium. We study the Cu2+-mediated susceptibility of human LDL to oxidation and the levels of free radical products of LDL lipoperoxidation in LDL particles from patients with atherosclerosis after 3 months treatment with natural antioxidants vitamin E as well as during 6 months administration of HMG-CoA reductase inhibitors such as pravastatin and cerivastatin in monotherapy and in combination with natural antioxidant ubiquinone Q10 or synthetic antioxidant probucol in a double-blind placebo-controlled trials. The 3 months of natural antioxidant vitamin E administration (400 mg daily) to patients did not increase the susceptibility of LDL to oxidation. On the other hand, synthetic antioxidant probucol during long-time period of treatment (3-6 months) in low-dose (250 mg daily) doesn't change the lipid metabolism parameters in the blood of patients but their high antioxidant activity was observed. Really, after oxidation of probucol-contained LDL by C-15 animal lipoxygenase in these particles we identified the electron spin resonance signal of probucol phenoxyl radical that suggests the interaction of LDL-associated probucol with lipid radicals in vivo. We observed that 6 months treatment of patients with pravastatine (40 mg daily) or cerivastatin (0.4 mg daily) was followed by sufficiently accumulation of LDL lipoperoxides in vivo. In contrast, the 6 months therapy with pravastatin in combination with ubiquinone Q10 (60 mg daily) sharply decreased the LDL initial lipoperoxides level whereas during treatment with cerivastatin in combination with probucol (250 mg daily) the LDL lipoperoxides concentration was maintained on an invariable level. Therefore, antioxidants may be very effective in the prevention of atherogenic oxidative modification of LDL during HMG-CoA reductase inhibitors therapy.