Background The risk of cardiovascular disease is closely connected to adipose tissue inflammation. The links between cardiovascular risk predictors and pro and anti-inflammatory macrophages in human adipose tissue were analysed to gain an insight into the pathophysiology of cardiovascular disease. Design Subcutaneous and visceral adipose tissues were obtained from 79 subjects, 52 living kidney donors (during nephrectomy) and 27 patients with peripheral artery disease (during arterial tree reconstruction). Methods Macrophage subsets were isolated from adipose tissues and analysed by flow cytometry using CD14, CD16, CD36 and CD163 monoclonal antibodies. The mutually adjusted differences of phagocytic pro-inflammatory (CD14 + CD16 + CD36high), anti-inflammatory (CD14 + CD16-CD163+) and transitional subsets of macrophages were analysed in relation to cardiovascular predictors (sex, age, body mass index, smoking, hypercholesterolaemia, hypertension and statin treatment). Results Age, male sex and hypercholesterolaemia were closely positively associated with the phagocytic pro-inflammatory macrophage subset in visceral adipose tissues. Interestingly, the proportion of phagocytic pro-inflammatory macrophages was relevantly decreased by statin therapy. A strong positive association of body mass index to the phagocytic pro-inflammatory subset was found in subcutaneous adipose tissues only. A minor transitional subpopulation, CD14 + CD16 + CD36lowCD163+, increased with age in both adipose tissues. This transitional subpopulation was also negatively associated with obesity and hypercholesterolaemia in visceral adipose tissues. Conclusion An effect of cardiovascular risk predictors on adipose tissue macrophage subpopulations was revealed. Interestingly, while age, male sex and hypercholesterolaemia were connected with the pro-inflammatory macrophage subpopulation in visceral adipose tissues, body mass index had a prominent effect in subcutaneous adipose tissues only. A decreasing effect of statins on these pro-inflammatory macrophages was documented.

• Klíčová slova
• Cardiovascular risk factors, adipose tissue, inflammation, macrophage, statins,
• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• fagocytóza MeSH
• fenotyp MeSH
• hypercholesterolemie krev   farmakoterapie   patologie   MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy účinky léků   metabolismus   patologie   MeSH
• mediátory zánětu krev   MeSH
• nitrobřišní tuk účinky léků   metabolismus   patologie   MeSH
• onemocnění periferních arterií krev   patologie   chirurgie   MeSH
• podkožní tuk účinky léků   metabolismus   patologie   MeSH
• prognóza MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• statiny terapeutické užití   MeSH
• studie případů a kontrol MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• mediátory zánětu MeSH
• statiny MeSH

Prague hereditary hypercholesterolemic (PHHC) rat - rat strain crossbred from Wistar rats - is a model of hypercholesterolemia induced by dietary cholesterol. Importantly, no bile salts and/or antithyroid drugs need to be added to the diet together with cholesterol to induce hypercholesterolemia. PHHC rats have only modestly increased cholesterolemia when fed a standard chow and develop hypercholesterolemia exceeding 5 mmol/l on 2 % cholesterol diet. Most of the cholesterol in hypercholesterolemic PHHC rats is found in VLDL that become enriched with cholesterol (VLDL-C/VLDL-TG ratio > 1.0). Concurrently, both IDL and LDL concentrations rise without any increase in HDL. PHHC rats do not markedly differ from Wistar rats in the activities of enzymes involved in intravascular remodelation of lipoproteins (lipoprotein and hepatic lipases and lecithin:cholesterol acyltransferase), LDL catabolism, cholesterol turnover rate and absorption of dietary cholesterol. The feeding rats with cholesterol diet results in development of fatty liver in spite of suppression of cholesterol synthesis. However, even though cholesterolemia in PHHC rats is comparable to human hypercholesterolemia, the PHHC rats do not develop atherosclerosis even after 6 months on 2 % cholesterol diet. Importantly, the crossbreeding experiments documented that hypercholesterolemia of PHHC rats is polygenic. To identify the genes that may be involved in pathogenesis of hypercholesterolemia in this strain, the studies of microarray gene expression in the liver of PHHC rats are currently in progress.

• MeSH
• ateroskleróza genetika   metabolismus   patologie   MeSH
• cholesterol dietní škodlivé účinky   MeSH
• cholesterol krev   MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• hybridizace genetická MeSH
• hypercholesterolemie krev   genetika   patologie   MeSH
• játra metabolismus   patologie   MeSH
• krysa rodu Rattus MeSH
• lipoproteiny krev   MeSH
• modely nemocí na zvířatech MeSH
• multifaktoriální dědičnost MeSH
• potkani Wistar MeSH
• progrese nemoci MeSH
• ztučnělá játra genetika   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cholesterol dietní MeSH
• cholesterol MeSH
• lipoproteiny MeSH

Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol-lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection against myocardial ischemia-reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff-perfused hearts of healthy control (C) and diabetic-hypercholesterolemic (D-H; streptozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium staining). Postischemic recovery of left ventricular developed pressure (LVDP) in animals with D-H was improved by simvastatin therapy (62.7+/-18.2 % of preischemic values vs. 30.3+/-5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperfusion. Likewise, simvastatin shortened the duration of ventricular tachycardia (10.2+/-8.1 s and 57.8+/-29.3 s in C and D-H vs. 143.6+/-28.6 s and 159.3+/-44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C. The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the improvement of contractile recovery and attenuation of lethal I/R injury in both, healthy and diseased individuals.

• MeSH
• cholesterol krev   MeSH
• experimentální diabetes mellitus komplikace   farmakoterapie   patologie   patofyziologie   MeSH
• hypercholesterolemie komplikace   farmakoterapie   patologie   patofyziologie   MeSH
• infarkt myokardu etiologie   patologie   patofyziologie   prevence a kontrola   MeSH
• ischemická choroba srdeční etiologie   patologie   patofyziologie   prevence a kontrola   MeSH
• kardiotonika farmakologie   MeSH
• komorový tlak (srdce) účinky léků   MeSH
• kontrakce myokardu účinky léků   MeSH
• krysa rodu Rattus MeSH
• myokard patologie   MeSH
• obnova funkce MeSH
• perfuze MeSH
• potkani Wistar MeSH
• simvastatin farmakologie   MeSH
• srdeční arytmie etiologie   patologie   patofyziologie   prevence a kontrola   MeSH
• statiny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholesterol MeSH
• kardiotonika MeSH
• simvastatin MeSH
• statiny MeSH

Early stages of atherogenesis are characterized by the overexpression of cell adhesion molecules with the subsequent accumulation of macrophages, smooth muscle cells and proliferation of extracellular matrix in arterial intima. The quantification of atherogenic changes is necessary for the objective evaluation of the atherogenic process. The purpose of this study was to introduce stereological methods that may be used for the quantification of immunohistochemical staining, namely intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Twenty-four New Zealand White rabbits were subdivided into the three groups. Eighteen rabbits received a 0.4% cholesterol diet for 1, 2 and 3 months, respectively. Stereological principles of the systematic uniform random sampling and the point-counting method were applied for the quantification. Stereological analysis showed that VCAM-1 and ICAM-1 were upregulated during the consumption of high cholesterol diet and that VCAM-1, but not ICAM-1, has a considerable role in the formation of early atherosclerotic lesions. Stereological methods proved to be useful for the quantification of immunohistochemistry and can be used for an objective characterization of atherogenic changes in atherosclerosis.

• MeSH
• aorta thoracica účinky léků   metabolismus   patologie   MeSH
• arterioskleróza etiologie   metabolismus   patologie   MeSH
• časové faktory MeSH
• cévní buněčněadhezivní molekula-1 metabolismus   MeSH
• cévní endotel účinky léků   metabolismus   patologie   MeSH
• cholesterol dietní aplikace a dávkování   MeSH
• cholesterol krev   MeSH
• dieta aterogenní MeSH
• hypercholesterolemie krev   etiologie   patologie   MeSH
• imunoenzymatické techniky MeSH
• králíci MeSH
• mezibuněčná adhezivní molekula-1 metabolismus   MeSH
• mikroskopie metody   MeSH
• modely nemocí na zvířatech MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cévní buněčněadhezivní molekula-1 MeSH
• cholesterol dietní MeSH
• cholesterol MeSH
• mezibuněčná adhezivní molekula-1 MeSH

Loss of apolipoprotein E synthesis causes increased serum cholesterol concentrations and the sensitivity to high-fat diet in mice. We analyzed the changes in lipoprotein and hepatic structures in apolipoprotein E-deficient mice kept on control diet and cholesterol diets. Basal cholesterolemia of heterozygous (+/-) mice (2.2+/-0.28 mmol/l) was the same compared to wild-type (+/+) mice (2.3+/-0.15 mmol/l), but was lower compared to homozygous (-/-) mice (10.3+/-1.40 mmol/l). In +/- mice, cholesterolemia rose to 3.2 mmol/l on cholesterol diet and to 9 mmol/l on cholate diet, to 3 mmol/l and 3.6 mmol/l in +/+ mice, and to 23.4 mmol/l and 70.5 mmol/l in -/- mice, respectively. While the ratio of cholesterol/triglyceride concentrations in VLDL, IDL and LDL fractions was not increased in +/- mice and +/+ mice, it was increased in -/- mice on control diet. On the cholesterol diet, this ratio rose and was dramatically increased by cholate diet in all groups of mice. Even though cholate supplementation increased cholesterol concentration, it led to substantial toxic changes in hepatic morphology of all animals. In conclusion, one functional apo E allele in +/- mice is effective in keeping serum cholesterol concentrations in normal range on a control diet, but not on the cholesterol and cholate diets.

• MeSH
• aplikace orální MeSH
• apolipoproteiny E nedostatek   MeSH
• choláty aplikace a dávkování   MeSH
• cholesterol dietní metabolismus   MeSH
• cholesterol krev   MeSH
• dieta metody   MeSH
• hypercholesterolemie krev   patologie   MeSH
• játra účinky léků   patologie   MeSH
• lipoproteiny krev   MeSH
• myši knockoutované MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• apolipoproteiny E MeSH
• choláty MeSH
• cholesterol dietní MeSH
• cholesterol MeSH
• lipoproteiny MeSH

We present 12 patients with 20 plexiform xanthomatous tumors (PXTs). All patients were male. Patient ages ranged from 20 to 59 years (mean 45 years). Clinical information was available for 11 (92%) patients. Only one patient with markedly elevated cholesterol levels had a family history of hypercholesterolemia; none of the others had a family or personal history of diabetes mellitus, hypercholesterolemia, or hyperlipoproteinemia. Three patients had markedly elevated serum triglyceride levels. The tumors were solitary in seven patients and multiple in five patients: three patients had two tumors, one presented had three, and one had four. PXTs were located on the knee (n = 8), elbow (n = 5), foot or hand (n = 3), and one each on the Achilles tendon, buttock, toe, and back. PXT was white to yellow in color and ranged in size from 0.7 to 5 cm (mean 2.7 cm). The tumors were located in the dermis and subcutis, had a distinctive plexiform arrangement, and were composed of various admixtures of uniform epithelioid and xanthomatous cells. All tumors in patients with solitary or multiple lesions had a plexiform architecture. Most of the nodules of the plexiform pattern of PXTs measured 0.5-2 mm. Rarely cholesterol clefts, necrosis, sparse inflammation, and multinucleated Touton giant cells were present. In two patients with multiple tumors, the PXT completely lacked the xanthoma cells and thus resembled an epithelioid lesion. Immunohistochemically, all lesions were KP1 (CD68) and vimentin positive and lysozyme, S-100 protein, HMB-45, epithelial membrane antigen, cytokeratins, factor VIIIrag, CD34, muscle-specific actin, alpha-smooth muscle actin, desmin (D33), desmin (Der-11), chromogranin, synaptophysin, neurofilament protein, and glial fibrillary acidic protein negative. Two patients with multiple lesions noted recurrences over 10 years. With the exception of one patient who died of an unknown cause, all 10 patients with follow-up were alive, some with residual disease, over a mean of 9 years (range 1-25 years). Some PXTs may represent a morphologic variant of tuberous or tendinous xanthoma, yet its exclusive occurrence in men, absence of personal/familial hyperlipemia/hypercholesterolemia in some patients, and relative paucity of inflammation and cholesterol clefts may make this a distinctive entity.

• MeSH
• antigeny diferenciační myelomonocytární analýza   MeSH
• CD antigeny analýza   MeSH
• dospělí MeSH
• hypercholesterolemie patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory měkkých tkání chemie   patologie   MeSH
• xantomatóza patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD68 antigen, human MeSH Prohlížeč

Calcium ions act as intracellular messengers in numerous cellular functions and participate also in the development of the atherosclerotic process. Calcium homeostasis could be an important factor in the development of atherosclerosis. One of the drugs which interferes with calcium homeostasis are calcium channel blockers. A number of studies have investigated the possibility whether these drugs may be also useful for prevention of atherosclerosis. However, other investigators have reported that calcium channel blockers did not suppress the atherosclerotic process. In our work we assumed the direct influence of calcium channel blockers on transendothelial transport mechanisms. Therefore we decided to investigate the influence of verapamil, diltiazem and isradipine on the development of experimental atherosclerosis in rabbits. Verapamil administered twice daily, 0.125 mg per kg s. c., reduced the size of atheromatous plaques in the thoracic aorta and the level of total cholesterol and triglycerides in serum. This above effect was not present after administration of diltiazem in doses of 1.0 mg per kg and isradipine 1.25 mg per kg twice daily subcutaneously. Our conclusion is that the anti-atherosclerotic effect of calcium channel blockers is dose-dependent. It is not clear whether this effect takes place in the plasma compartment and/or in the intracellular compartment.

• MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• cévní endotel metabolismus   patologie   MeSH
• histocytochemie MeSH
• hypercholesterolemie metabolismus   patologie   MeSH
• králíci MeSH
• metabolismus lipidů * MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• blokátory kalciových kanálů MeSH

Histologic sections of the aortic arches from guinea pigs were stained with nile red to verify the possibility of quantitating the earliest changes in the arterial wall. Nile red fluorescence intensity was quantitated by conversion to electric signal. Fluorescence in a group fed cholesterol and casein was significantly higher than that in a control group. Its dependence on the logarithm of serum cholesterol concentrations between 1.33 and 7.67 mmol/l was found. Small fluorescence intensity differences far beyond the possibilities of visual observation were detected by the method.

• MeSH
• aorta thoracica patologie   MeSH
• fluorescenční barviva * MeSH
• hypercholesterolemie patologie   MeSH
• morčata MeSH
• oxaziny * MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluorescenční barviva * MeSH
• nile red MeSH Prohlížeč
• oxaziny * MeSH