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
This review focuses on current knowledge of leptin biology and the role of leptin in various physiological and pathophysiological states. Leptin is involved in the regulation of body weight. Serum leptin can probably be considered as one of the best biological markers reflecting total body fat in both animals and humans. Obesity in man is accompanied by increased circulating leptin concentrations. Gender differences clearly exist. Leptin is not only correlated to a series of endocrine parameters such as insulin, glucocorticoids, thyroid hormones, testosterone, but it also seems to be involved in mediating some endocrine mechanisms (onset of puberty, insulin secretion) and diseases (obesity, polycystic ovary syndrome). It has also been suggested that leptin can act as a growth factor in the fetus and the neonate., R. Janečková., and Obsahuje bibliografii
Lipid peroxidation of rat cerebral cortex membranes was induced by Fe2+/ADP and ascorbate. The rate of Na+/K+-ATPase inhibition was correlated with the increase of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes (CD) and with membrane fluidity changes. Our data showed that membrane fluidity changes (evaluated by fluorescence steady-state anisotropy measurements) can participate in Na+/K+-ATPase inhibition during the initial period of lipid peroxidation process, whereas during the following period the enzyme inhibition correlates only with TBARS and CD production., H. Rauchová, Z. Drahota, J. Koudelová., and Obsahuje bibliografii
Endothelial dysfunction may be considered as the interstage between risk factors and cardiovascular pathology. An imbalance between the production of vasorelaxing and vasoconstricting factors plays a decisive role in the development of hypertension, atherosclerosis and target organ damage. Except vasorelaxing and antiproliferative properties per se, nitric oxide participates in antagonizing vasoconstrictive and growth promoting effects of angiotensin II, endothelins and reactive oxygen species. Angiotensin II is a potent activator of NAD(P)H oxidase contributing to the production of reactive oxygen species. Numerous signaling pathways activated in response to angiotensin II and endothelin-1 are mediated through the increased level of oxidative stress, which seems to be in casual relation to a number of cardiovascular disturbances including hypertension. With respect to the oxidative stress, the NO molecule seems to be of ambivalent nature. On the one hand, NO is able to reduce generation of reactive oxygen species by inhibiting association of NAD(P)H oxidase subunits. On the other hand, when excessively produced, NO reacts with superoxides resulting in the formation of peroxynitrite, which is a free radical deteriorating endothelial function. The balance between vasorelaxing and vasoconstricting substances appears to be the principal issue for the physiological functioning of the vascular bed., O. Pecháňová, F. Šimko., 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
Rheological, haemostatic, endothelial and platelet abnormalities appear to play a role in the thrombotic complications of hypertension. This prothrombotic/hypercoagulable state in hypertension may contribute to the increased risk and severity of target organ damage. It can be induced by the activated reninangiotensin system (RAS), with abnormalities in endothelial and platelet function, coagulation and fibrinolysis. Treatment of uncomplicated essential hypertension by RAS targeting antihypertensive therapy could result in a reversal of prothrombotic abnormalities, contributing to a reduction of thrombosis-related complications. Since angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have two distinct mechanisms of RAS interruption, it is hypothesized that each therapy might have different impact on the prothrombotic state in hypertensive patients. Some studies demonstrate a beneficial effect of both ACE inhibitors and ARBs on prothrombotic state, in addition to their efficacy to normalize elevated blood pressure. The potentially antithrombotic effect of the RAS inhibiting agents may in turn support the preservation of cardiovascular function. Available data may offer an additional explanation for the efficacy of the RAS targeting agents in the prevention of cardiovascular events in patients with atherosclerotic vascular disease., A. Remková, M. Remko., and Obsahuje bibliografii a bibliografické odkazy
This review summarizes recent trends in the construction of bioartificial vascular replacements, i.e. hybrid grafts containing synthetic polymeric scaffolds and cells. In these advanced replacements, vascular smooth muscle cells (VSMC) should be considered as a physiological component, although it is known that activation of the migration and proliferation of VSMC plays an important role in the onset and development of vascular diseases, and also in re stenosis of currently used vascular grafts. Therefore, in novel bioartificial vascular grafts, VSMCs should be kept in quiescent mature contractile phenotype. This can be achieved by (1) appropriate physical and chemical properties of the material, such as its chemical composition, polarity, wettability, surface roughness and topography, electrical charge and conductivity, functionalization with biomolecules and mechanical properties, (2) appropriate cell culture conditions, such as composition of cell culture media and dynamic load, namely cyclic strain, and (3) the presence of a confluent, mature, semipermeable, non-thrombogenic and non-immunogenic endothelial cell (EC) barrier, covering the luminal surface of the graft and separating the VSMCs from the blood. Both VSMCs and ECs can also be differentiated from stem and progenitor cells of various sources. In the case of degradable scaffolds, the material will gradually be removed by the cells and will be replaced by their own new extracellular matrix. Thus, the material component in advanced blood vessel substitute s acts as a temporary scaffold that promotes regeneration of the damaged vascular tissue., M. Pařízek, K. Novotná, L. Bačáková., and Obsahuje bibliografii a bibliografické odkazy
Transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel activated by capsaicin, a pungent substance from chili peppers. It is considered to act as an integrator of various physical and chemical nociceptive stimuli, as it can be gated by noxious heat (>43ºC), low pH (protons) and also by recently described endogenous lipids. The structure and function of TRPV1 receptors was vigorously studied, especially since its cloning in 1997. However, most of the research was pointed towards the role of TRPV1 receptors in the peripheral tissues. Mounting evidence now suggests that TRPV1 receptors on the central branches of dorsal root ganglion neurons in the spinal cord may play an important role in modulation of pain and nociceptive transmission. The aim of this short review was to summarize the knowledge about TRPV1 receptors in the spinal cord dorsal horn, preferentially from morphological and electrophysiological studies on spinal cord slices and from in vivo experiments., D. Špicarová, J. Paleček., and Obsahuje bibliografii a bibliografické odkazy
The tissue factor (TF) is one of the most important regulators of arterial thrombosis. Because arterial thrombosis is the pathophysiologic background of acute coronary syndrome, the possible impact of blocking the arterial thrombosis on its onset is a challenging problem. The investigations of TF brought a new concept of “cell-based coagulation model” which highlighted the question of blood-borne TF as a source of TF in circulating blood. In this review we summarize essential information on the pathophysiology, molecular structure, expression and distribution of TF and we propose a novel concept of blood-borne TF, suggesting the possibilities of inhibition of the coagulation cascade with newly synthetized drugs., M. A. Malý, P. Tomašov, P. Hájek, P. Blaško, I. Hrachovinová, P. Salaj, J. Veselka., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to explore changes in plasma vascular endothelial growth factor (VEGF) in aged patients who undergone transcatheter aortic valve implantation or balloon angioplasty for the treatment of aortic stenosis. Plasma VEGF was measured in subjects with diabetes mellitus type 2 (DM) (n=21, age 79.2±1.6 years) and in non-diabetic subjects (non-DM) (n=23, age 84.4±0.7 years), using an ELISA kit. Before the procedure plasma levels of VEGF were significantly lower in DM than in non-DM patients (P<0.05). Plasma VEGF significantly increased in both groups (DM and non-DM) 24 h (387±64 vs. 440±30 pg/ml, P<0.05) and 72 h (323±69 vs. 489±47 pg/ml, P<0.05) after the endovascular procedure. However, the VEGF in DM patients was significantly lower compared to non-DM subjects up to one month after the endovascular procedure (283±47 vs. 386±38 pg/ml, P<0.05). We conclude that increased plasma VEGF in aged patients associates with atherosclerotic aortic valve stenosis. In spite of that plasma VEGF in DM was constantly significantly lower than in non diabetic patients, both before and after the endovascular procedure, possibly reflecting a disturbance of angiogenic/antiangiogenic balance in diabetes., V. Bláha, J. Šťásek, J. Bis, J. Fortunato, C. Andrýs, V. Pavlík, P. Polanský, M. Brtko, L. Sobotka., and Obsahuje bibliografii