It is now generally accepted that adipose tissue acts as an endocrine organ producing a number of substances with an important role in the regulation of food intake, energy expenditure and a series of metabolic processes. Adiponectin is a recently discovered protein produced exclusively by adipocytes. A number of studies have shown that obesity, insulin resistance and atherosclerosis are accompanied by decreased adiponectin levels and that adiponectin replacement under experimental settings is able to diminish both insulin resistance and atherosclerosis. The aim of this review is to summarize the current knowledge about the physiology and pathophysiology of adiponectin and to discuss its potential in the treatment of insulin resistance and atherosclerosis.
Aldosterone plays a key role in maintaining the homeostasis of the whole organism. Under some circumstances, aldosterone can contribute to the progression of cardiovascular diseases, including coronary artery disease. This study demonstrates that aldosterone associates negatively with some lipidogram parameters and positively with the concentration of homocysteine. These associations are characteristic for coronary artery disease and are not present in control subjects. The findings also indicate that in vitro aldosterone stimulates homocysteine production by rat adrenal glands, which may explain the associations observed with coronary artery disease. Moreover, we have found that aldosterone significantly modulates in vitro platelet reactivity to arachidonate and collagen - aldosterone increases the pro-aggregatory action of collagen, but decreases the pro-aggregatory potential of arachidonate. Therefore, the findings of these in vitro and ex vivo experiments indicate the existence of new pathways by which aldosterone modulates lipid- homocysteine- and platelet-dependent atherogenesis., K. Karolczak, P. Kubalczyk, R. Glowacki, R. Pietruszynski, C. Watala., and Seznam literatury
Diabetes mellitus is associated with an increased prevalence of endothelial dysfunction and development of atherosclerotic vascular diseases. We demonstrate here that hyperglycemia results in the expression of adhesion molecules on endothelial cells in vitro. Incubation of human umbilical vein endothelial cells (HUVEC) in a culture medium with 11.0 mM, 16.5 mM and 22.0 mM glucose concentrations induced the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1). This effect was detectable after 24 h incubation of HUVEC with a high glucose concentration. The effect of high glucose concentration on TNF- induced expression of ELAM-1, VCAM-1 and ICAM-1 was negligible, if at all. These results show that even a short-term exposure of endothelial cells (ECs) to high glucose concentration leads to their activation associated with increased expression of adhesion molecules such as ELAM-1, VCAM-1 and ICAM-1.
Impressive advances in molecular genetic techniques allow to analyze the effects of natural selection on the development of human genome. For example, the trend towards blonde hair and blue eyes was documented. The approach to analyze possible effects of natural selection on the evolution of recent phenotypes with high risk of cardiovascular disease has not been described yet. A possible effect on the evolution of two main risk factors - hypercholesterolemia and hypertension - is presented. The close relationship of non-HDL cholesterol blood concentration to the proportion of pro-inflammatory macrophages in human visceral adipose tissue might be a result of long-lasting natural selection. Individuals with higher proportion of this phenotype might also display a higher ability to fight infection, which was very common in human setting from prehistory until Middle Ages. Successful battle against infections increased the probability to survive till reproductive age. Similar hypothesis was proposed to explain frequent hypertension in African Americans. A long-lasting selection for higher ability to conserve sodium during long-term adaptation to low sodium intake and hot weather was followed by a short-term (but very hard) natural selection of individuals during transatlantic slave transport. Only those with very high capability to retain sodium were able to survive. Natural selection of phenotypes with high plasma cholesterol concentration and/or high blood pressure is recently potentiated by high-fat high-sodium diet and overnutrition. This hypothesis is also supported by the advantage of familial hypercholesterolemia in the 19th century (at the time of high infection disease mortality) in contrast to the disadvantage of familial hypercholesterolemia during the actual period of high cardiovascular disease mortality., R. Poledne, J. Zicha., and Seznam literatury
Atherogenic lipoproteins can cause endothelial dysfunction in the initial stage of atherogenesis. In our study we examined 134 patients with defined hyperlipoproteinemia (non-HDL cholesterol > 4.1 mmol/l or triglycerides > 2.5 mmol/l or taking any of lipid lowering drugs) – 94 men and 40 women. The subgroup of controls of comparable age contained 54 normolipidemic individuals – 30 men and 24 women. Patients with hyperlipoproteinemia revealed significantly lower ability of endothelium-dependent flow-mediated vasodilation (EDV) measured on brachial artery (4.13±3.07 vs. 5.41±3.82 %; p=0.032) and higher carotid intima media thickness than normolipidemic controls (0.68±0.22 vs. 0.58±0.15 mm; p=0.005). In regression analysis, EDV correlated significantly with plasma concentrations of oxLDL (p<0.05) HDL-cholesterol (p<0.05), Apo A1 (p<0.05), ATI (p<0.01) and non-HDL cholesterol (p<0.05). Patients with hyperlipoproteinemia showed higher plasma levels of oxLDL (65.77±9.54 vs. 56.49±7.80 U/l; p=0.015), malondialdehyde (0.89±0.09 vs. 0.73±0.08 µmol/l; p=0.010) and nitrites/nitrates (20.42±4.88 vs. 16.37±4.44 µmol/l; p=0.018) indicating possible higher long-term oxidative stress in these patients.
The role of adhesive selectin molecules in the process of atherogenesis is an open question. These molecules are known as markers of atherosclerosis activity, however, only some biological mechanisms are known up to now. In this study we examined the levels of soluble forms of E-, P-selectin and monocyte chemotactic protein (MCP-1) in the process of extracorporeal cholesterol elimination by LDL-apheresis. We measured the levels of sE-, sP-selectin and MCP-1 in the plasma before and after LDL-apheresis and in the washout solution from immunoabsorption columns Lipopak. Eighty measurements were performed repeatedly in 6 patients with severe familial hypercholesterolemia (FH) on long-term LDL-apheresis treatment. Before the procedure P-selectin levels were 204±179 ng/ml, E-selectin 32.1±33.7 ng/ml, MCP-1 323.8±121 pg/l, whereas after the procedure we found P-selectin levels 131.6±34 ng/ml, E-selectin 33.1±51 ng/ml, and MCP-1 200.4±15 pg/l. Levels of P- selectin were increased in the blood of patients with FH in spite of long-term intensive extracorporeal LDL-elimination, documenting thus the activity of atherosclerosis. The levels of
P-selectin and MCP-1 decreased significantly after the hypolidemic procedure and could be used as another marker showing the effectivity of the extracorporeal LDL-cholesterol elimination (immediately after the procedure), and, after further verification, may serve as a marker for controlling the therapy efficacy.
The aim of this study was to observe the effect of folate and antioxidants alone on homocysteine levels and oxidative stress markers, and to evaluate whether their co-administration promotes their effects. One hundred patients with hyperhomocysteinemia were randomized into four equal groups, which were then treated with folate, antioxidants or
folate plus antioxidants for 2 months; group IV was a control group. Serum homocysteine, folate and oxidative stress markers were measured before the study, at the end of folate and/or antioxidants administration and 3 months later. Folate caused a significant decrease in homocysteine concentration. Antioxidants did not influence homocysteine concentration, but they improved the antioxidative defense (plasma antioxidant capacity and intraerythrocyte
glutathione were increased) and partially prevented lipid peroxidation (malondialdehyde level was slightly decreased). Supplementation with folate had a similar effect on intracellular glutathione and plasma malondialdehyde. Simultaneous administration of folate and antioxidants did not show any additive effect with the exception of a slower decrease of folate concentration after its supplementation had been discontinued. Folate may be considered as an effective antioxidant in patients with hyperhomocysteinemia; this can be a result of decreased production of free radicals due to a reduced level of homocysteine. Its antioxidative effect cannot be promoted by co-administration of antioxidants.