The gene for connexin 37 (Cx37) is considered to be one of the candidate genes for cardiovascul ar disease. We evaluated the association between Cx37 (1019C>T) gene polymorphism (Pro319Ser) and ankle brachial blood pressure index (ABI) in women with type 1 (n=178) and ty pe 2 (n=111) diabetes, and in women from general population (n=862). All women were genotyped for Cx37 polymorphism. In addition to traditional cardiovascular risk factors, ABI was analyzed. In women with type 1 diabetes, ABI significantly decreased from TT to CC carriers (p for trend= 0.008). A similar trend was seen in women with type 2 diabetes (p=0.050) and in women with waist circumference above 75 th percentile (94 cm; n=208) of the general population (p=0.049). The gene for Cx37 was associated with subclinical atherosclerosis in women with type 1 and 2 diabetes and in women with advanced central obesity. The presence of C allele indicated increased risk., J. Piťha, J. A. Hubáček, P. Piťhová., and Obsahuje bibliografii
Increased circulating adhesion molecules in patients with obesity play an important role in the development of endothelial dysfunction/atherosclerosis. The aim of this study was to assess the contribution of various fat depots to the production of adhesion molecules in obesity. 12 women with 1st and 2nd degree of obesity, 13 women with 3rd degree of obesity and 14 lean age-matched women were included into study. Circulating levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were measured by Luminex kits. mRNA expression of ICAM-1, VCAM-1, E-selectin, monocyte chemoattractant protein-1 (MCP-1), and CD68 in subcutaneous (SAT) and visceral adipose tissue (VAT) was measured by RT-PCR; ICAM-1 and VCAM-1 protein levels by Luminex kits, normalized to protein content. Obesity increased ICAM-1 and VCAM-1 mRNA expression and protein levels and CD68 mRNA expression in VAT. Expression of E-selectin and MCP-1 did not significantly differ between groups. Expression of ICAM-1 and VCAM-1 positively correlated with expression of CD68 in both adipose depots. In VAT, ICAM-1 and VCAM-1 expression and protein levels positively correlated with BMI. Obesity was associated with increased adhesion molecules mRNA expression and protein levels in VAT, but not in SAT. Increased adhesion molecules production in visceral fat may provide a novel direct link between visceral adiposity and increased risk of cardiovascular complications., L. Bošanská ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Ferritin and increased iron stores first appea red on the list of cardiovascular risk factors more than 30 years ago and their causal role in the pathogenesis of atherosclerosis has been heavily discussed since the early 1990s. It seems that besides traditional factors such as hyperlipoprotein emia, hyp ertension, diabetes mellitus, obesity, physical inactivity, smoking and family history, high iron stores represent an additional parameter that could modify individual cardiovascular risk. The role of iron in the pathogenesis of atherosclerosis was origina lly primarily associated with its ability to cataly ze the formation of highly reactive free oxygen radicals and the oxidation of atherogenic lipoproteins. Later, it became clear that the mechanism is more complex. Atherosclerosis is a chronic fibroprolife rative inflammatory process and iron, through increased oxidation stress as well as directly, can control both native and adaptive immune responses. Within the arterial wall, iron affects all of the cell types that participate in the atherosclerotic proces s (monocytes/macrophages, endothelial cells, vascular smooth muscle cells and platelets). Most intracellular iron is bound in ferritin, whereas redox-active iron forms labile iron pool. Pro-inflammatory and anti-inflammatory macrophages within arterial plaque differ with regard to the amount of intracellular iron and most probably with regard to their labile iron pool. Yet, the relation between plasma ferritin and intracellular labile iro n pool has not been fully clarified. Data from population studies document that the consumption of meat and lack of physical activity contribute to increased iron stores. Patients with hereditary h emochromatosis, despite extreme iron storage, do not show i ncreased manifestation of atherosclerosis probably due to the low expression of hepcidin in macrophages., P. Kraml., and Obsahuje bibliografii
Dihydrotestosterone (DHT) originates via irreversible reduction of testosterone by catalytic activity of 5α-reductase enzyme and it is demonstratively the most effective androgen. Androgens influence adipose tissue in men either directly by stimulation of the androgen receptor or indirectly, after aromatization, by acting at the estrogen receptor. DHT as a non-aromatizable androgen could be responsible for a male type fat distribution. The theory of non-aromatizable androgens as a potential cause of a male type obesity development has been studied intensively. However, physiological levels of DHT inhibit growth of mature adipocytes. In animal models, substitution of DHT in males after gonadectomy has a positive effect on body composition as a testosterone therapy. Thus, DHT within physiological range positively influences body composition. However, there are pathological conditions with an abundance of DHT, e.g. androgenic alopecia and benign prostatic hyperplasia. These diseases are considered as ri sk factors for development of metabolic syndrome or atherosclerosis. In obese people, DHT metabolism in adipose tissue is altered. Local abundance of non- aromatizable androgen has a nega tive effect on adipose tissue and it could be involved in pathogenesis of metabolic and cardiovascular diseases. Increased DHT levels, compared to physiological levels, have negati ve effect on development of cardiovascular diseases. Difference between the effect of physiological and increased level brings about certain paradox., M. Dušková, H. Pospíšilová., and Obsahuje bibliografii a bibliografické odkazy
Traditionally, lecithinxholesterol acyltransferase (LCAT) role in the reverse cholesterol transport (RCT) has been considered "antiatherogenic" as the cholesterol esterification is the prerequisite for the formation of mature high density lipoprotein (HDL) particles and may create a gradient necessary for the flow of unesterified cholesterol (UC) from tissues to plasma. However, newer data suggest that a higher esterification rate is not necessarily protective. Here we review the available data on the role of LCAT in RCT and propose that the LCAT-mediated esterification of plasma cholesterol promotes RCT only in the presence of sufficient concentrations of HDL2 while this reaction may be atherogenic in the presence of high concentration of plasma low density lipoprotein (LDL) cholesteroL Thus, the "protective" or potentially "atherogenic" role of LCAT depends on the quality of HDL and concentration of LDL. This hypothesis is consistent with the known high predictive value of LDL/HDL cholesterol ratio.
Vascular stenosis is often described only by its percentage in both clinical and scientific praxis. Previous studies gave inconclusive results regarding the effect of stenosis eccentricity on its hemodynamic effect. The aim of this experimental study was to investigate and quantify the effect of stenosis severity and eccentricity on the pressure drop. A combination of pressure and flow measurements by Par ticle Imaging Velocimetry (PIV) method was used. Models of the same stenosis significance but with different levels of eccentricity were studied in vitro by PIV. This study has shown that stenosis asymmetry is associated with more profound pressure drop an d flow volume decrease. On the contrary, pressure drop and flow volume decrease were not further significantly influenced by the level of asymmetry. Hemodynamic changes associated with stenosis eccentricity must be taken into account in both clinical and s cientific studies., L. Novakova, J. Kolinsky, J. Adamec, J. Kudlicka, J. Malik., and Obsahuje bibliografii