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Background/Aims. Cholesterol takes part in atherogenesis and is therefore a crucial risk factor of coronary artery disease (CAD). Lipid metabolism is regulated by a number of genes, including circadian ones. Circadian genes participate in the regulation of vessel function and are associated with CAD, although their exact role in CAD pathogenesis remains unknown. The study was aimed to reveal the connection of circadian genes with various lipids of blood plasma.Methods. The study included Russian patients with CAD (N=250) confirmed by coronary angiography, and healthy donors without such lesions (N=137). All patients underwent thorough cardiologic examination due to suspected CAD. Genotyping of single nucleotide polymorphisms (SNP) was performed using MALDI-TOF minisequencing. We analyzed CLOCK (rs1801260), PER1 (rs2735611), PER2 (rs2304672), CRY1 (rs8192440), NPAS2 (rs11123857, AGT-3 (rs699), AGT-4 (rs4762), AGTR (rs5186), LIPC4 (rs1800588), MTHFR (rs1801133), PAI (rs1799889), CRP (rs1205) and some other genes. Pink software was used to analyze the associations.Results. We have found significant associations of atherosclerotic lesion of coronary arteries with polymorphisms of CRY1 (rs8192440), AGT-3 (rs699), AGT-4 (rs4762), LIPC4 (rs1800588), MTHFR (rs1801133), CRP (rs1205) with p-value <0.05, and strongest association of total plasma cholesterol level with CLOCK (rs1801260) gene polymorphism (p=0.003); low density lipoprotein (LDL) level with CLOCK (rs1801260, p=0.0006), PAI (rs1799889, p=0.01), CRP (rs1205, p=0.003); very low density lipoprotein (VLDL) level with AGTR (rs5186, p=0.006). We produced decision tree from variants associated with different cholesterol fractions using coronary defense as outcome, and area under ROC curve is 0.67±0.1.Conclusions. The obtained data suggest a complex role of circadian genes in CAD pathogenesis in respect of their involvement in lipid metabolism. CLOCK gene is associated with LDL and total cholesterol, but not with CAD, and may therefore indirectly influence the process of coronary atherosclerosis. Other noncircadian genes that connected with various lipid fractions also do not seem to have significant association with coronary atherosclerosis. The exception is CRP (rs1205), which is associated both with CAD and lipids. This finding requires further study. [ABSTRACT FROM PUBLISHER]

The CRX gene encoding the cone-rod homeobox protein is a specific photoreceptor transcription factor crucial for retinal function. Persons temporarily residing in the Arctic zone during the polar summer may suffer from disturbances associated with extremely high ambient illumination. These environmental changes are mediated by retinal photoreceptors; therefore, it is important to study the expression of retinal genes in order to assess individual capacities of sensory adaptation to polar day conditions., Purpose: To reveal the dynamics of CRX expression level in humans after a prolonged temporary exposure to polar day conditions., Material and Methods: The study included 6 pilots (males from 39 to 69 y.o.) who participated in the Arctic World Oceanic International Flight Sever Vash (West to East, from 62°N 74°E to 72°N 114°E). Samples of peripheral blood for RNA isolation were collected at the start and at the end of the flight. The level of mRNA in the samples was evaluated based on the data of quantitative real-time PCR of the CRX gene, as well as the b2M and TBP housekeeping genes (reference)., Results: Expression of the CRX gene in the studied group ( p <0.01) was revealed; the total average level of mRNA was about 3 times higher prior to, and approximately 7 times higher after normalization to the b2M gene. Five pilots had increased expression of the CRX gene within the range of -1.53 to -3.07 (Z-score of <0 before the flight and >0 after the flight). In one pilot, the level of CRX expression was higher at the start, but it reduced by the end of the circumnavigation flight., Conclusions: The results confirm the hypothesis that the CRX gene is expressed after a prolonged temporary exposure to polar day conditions. It was also revealed that during rapid adaptation, equal changes in the illumination of retinal photoreceptors lead to different individual dynamics of CRX expression.

Aim        To study temporal and spectral characteristics of heart rhythm variability (HRV) in night shift workers.Materials and methods       Along with traditional risk factors, conditions of labor contribute to development of cardiovascular morbidity, including night shift work, which can be associated with disorders of the autonomic regulation detected by analysis of HRV. This study included 100 healthy men. 74 of them were engaged in shift work, including 53 men with rotating shift work, 21 men with fixed night shifts, and 26 men with day-time work. HRV was analyzed by data of 5-min electrocardiogram recording (background recording and orthostatic test).Results   Night-shift workers had decreases in total power of regulation (ТР, SDNN) and in the parasympathetic branch (HF, pNN50). Rotating night-shift workers displayed significant decreases in SDNN and pNN50 and pronounced changes in the VLF / LF / HF ratio in the orthostatic test.Conclusion            In work with night shifts, the type of autonomic regulation differs from the "standard" functioning of the autonomic nervous system (ANS). This study showed different effects of night work regimens on HRV indexes. With the rotating shift work, the ANS dysregulation was more profound and was evident by a significant decrease in the ANS total tone and parasympathetic activity (SDNN, pNN50) compared to night shifts with fixed working hours. The excessive weakening of the parasympathetic component in the passive orthostatic test can be considered as an early marker for ANS maladaptation.

The aim of this study was to develop an artificial neural networks-based (ANNs) diagnostic model for coronary heart disease (CHD) using a complex of traditional and genetic factors of this disease. The original database for ANNs included clinical, laboratory, functional, coronary angiographic, and genetic [single nucleotide polymorphisms (SNPs)] characteristics of 487 patients (327 with CHD caused by coronary atherosclerosis, 160 without CHD). By changing the types of ANN and the number of input factors applied, we created models that demonstrated 64-94% accuracy. The best accuracy was obtained with a neural networks topology of multilayer perceptron with two hidden layers for models included by both genetic and non-genetic CHD risk factors., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The Decarto technique was used to study the orthogonal ECGs recorded in 23 subjects during parabolic flights (44 records). A parameter of the instantaneous decartograms, namely the activation area (AA), which is the total area of the depolarization front projection on the image sphere, was analyzed. We compared the values of AA during the periods of horizontal flight, upward parts of all parabolas, and the initial 10 s of microgravity of all parabolas. According to the characteristics of the vectorcardiograms and AA, all subjects were subdivided into 3 groups: with increased electric activity of the right ventricle (I), the left ventricle (II) and both ventricles (III). Changes of AA with change of gravitational levels in these groups showed some differences. In groups I and II, the AA of the initial part of the QRS complex increased during microgravity and decreased during hypergravity. In group III it decreased during microgravity and changed variously during hypergravity. The AA of the middle part of the QRS complex decreased during microgravity and increased during hypergravity, and these changes were more pronounced in group III. The changes of AA in groups I and II may be explained by the Brody effect. In group III, AA seems to be influenced by some additional factors, possibly by changes in the intramyocardial or intraventricular blood volume. The AA of the last part of the QRS complex increased during microgravity and decreased during hypergravity in all groups. This may be explained by an effect of mutual neutralization of depolarization fronts related to the changes of the QRS duration.(Fig. 3, Ref. 4)

With high resolution ultrasound we assessed endothelial function in subjects at risk of atherosclerosis. We used ACUSON 128XP/10 system with 7.0 MHz linear array transducer. Three groups of patients (pts) were studied: 12 patients with essential hypertension, ten patients with 2A familial hyperholesterolamia and ten controls without vascular risk factors. We measured the diameter of brachial artery at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilation), and after sublingual 0.01 mg nitroglycerin (causing endothelium-independent dilation). Flow-mediated dilation is not impaired in essential hypertension (9. 4%) compared with controls (9.5%) and impaired in patients with familial hyperholesterolaemia (3.0%). NTG-induced dilation is not impaired in familial hyperholesterolaemia (16.6%) and essential hypertension (14.5%) compared with controls (20.5%). The effect of hypolipidaemic influence (probucol and plasmapheresis) was assessed in a separate study. These results demonstrate the capability of ultrasound in detection of endothelial dysfunction, and suggest that endothelial dysfunction in patients with familial hyperholesterolaemia is one of the risk factors for atherosclerosis. The parameters of endothelial function may be used as markers of hypolipidemic influence on patients with hyperholesterolaemia., (Copyright 1998 Elsevier Science Ireland Ltd.)