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Interactive Influence of Genetic Effects and Effects of External Environment on Properties of Large Arteries in Relation to Sodium Management
Seidlerová, Jitka ; Filipovský, Jan (advisor) ; Widimský, Jiří (referee) ; Segers, Patrick (referee) ; Herijgers, Paul (referee)
In line with Guyton's work, the goal of our research was to explore in three European populations whether the properties of large arteries are associated with renal sodium handling, which itself changes with environmental factors and with variation in a large number of genes. Before engaging in the genetic analyses proper, we first studied the familial aggregation and the heritability of arterial properties. In all our analyses, we accounted for relatedness among participants and for covariables and confounders. In a first study, we compared the arterial characteristics and blood pressure (BP) in normotensive offspring of two normotensive parents (OFF/NT) and normotensive offspring, who had at least one hypertensive parent (OFF/HT). We measured peripheral pulse pressure (PPp) by conventional and 24-h ambulatory BP. A SphygmoCor device was used to determine the central (CAIx) and peripheral (PAIx) augmentation indexes, central pulse pressure (PPc), and aortic pulse wave velocity (aPWV). Compared with OFF/NT (n=59; 16 to 34 years of age), the OFF/HT (n=174; 17 to 40 years) had higher (0.14<P<0.0007) BP and PPp on conventional measurement (121/75 vs. 114/71 mm Hg and 46 vs. 42 mm Hg) as well as on 24-h ambulatory monitoring (118/70 vs. 114/67 mm Hg and 48 vs. 47 mm Hg). OFF/HT, compared with OFF/NT, also had...
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The role adipose tissue in development of insulin resistance and other metabolic disorders in patients with pheochromocytoma
Klímová, Judita ; Petrák, Ondřej (advisor) ; Kříž, Jan (referee) ; Mlíková Seidlerová, Jitka (referee)
Pheochromocytoma and functional paraganglioma (PPGL) are rare neuroendocrine tumors characterized by catecholamines overproduction, which give a rise to disorders of glucose, lipid, and energy metabolism. The role of adipose tissue in these processes remains unclear. Our aim was to determine the gene expression profile in subcutaneous and visceral adipose tissue of patients with PPGL focusing on endocrine functions of adipose tissue, occurrence of brown (BAT) and beige adipose tissue (BeAT), all in connection with other measured metabolic and energy parameters and levels of circulating adipokines. We demonstrate signs of UCP1-dependent norepinephrine induced thermogenesis connected with overexpression of DIO2 in retroperitoneal VAT of PPGL and higher expression of key transcriptional factors of brown/beige adipogenesis, namely PPARGC1α, CEBPB and PRDM16. However, classic murine BAT or BeAT gene signature in VAT of PPGL was not detected. In subcutaneous adipose tissue (SAT) of PPGL we found signs of possible BeAT transformation, however without simultaneously undergoing UCP1-dependent thermogenesis. We also demonstrate that patients with PPGL have higher serum levels of FGF21 compared to healthy controls and these levels do not differ from obese patients. Furthermore, successful tumor removal...
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The Metabolic Determinants of Central Arterial Stiffness
Karnosová, Petra ; Mlíková Seidlerová, Jitka (advisor) ; Bernat, Ivo (referee) ; Petrák, Ondřej (referee)
This dissertation demonstrates not only the classic hemodynamic and metabolic cardiovascular (CV) risk factors affecting arterial rigidity but also the soluble receptor for advanced glycation end-products (sRAGE) was studied. The stiffening of central arteries may precede the onset of manifest atherosclerosis, thus being a potential target for early prevention of cardiovascular disease. The actual guidelines of Czech society for hypertension recommend the measurement of aortic pulse wave velocity (aPWV) in hypertensive patients. The AGEs/RAGE complex participates in various stages of atherosclerosis/arterial stiffening. The soluble form of RAGE probably acts as a decoy for RAGE ligands and it is a naturally occurring inhibitor of toxic impact caused by AGE-RAGE action. It is suggested to be a potential marker of further chronic disease. This dissertation focuses on four publications investigating CV risk factors in two different population cohorts. We studied a random general population sample and offspring of patients with premature coronary heart disease sample compared to controls. In the general population we demonstrated that aPWV increased linearly with the rising numbers of individual metabolic syndrome risk factors (p for trend 0,0001). The levels of sRAGE were significantly positively...
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Large artery properties in primary and secondary - endocrine hypertension
Rosa, Ján ; Widimský, Jiří (advisor) ; Mlíková Seidlerová, Jitka (referee) ; Špinar, Jindřich (referee)
Arterial stiffness represented by carotid-femoral pulse wave velocity (PWV) is considered to be an independent cardiovascular risk factor. This study was focused on large artery properties investigation in specific forms of hypertension using applanation tonometer Sphygmocor (Atcor Medical). PWV was significantly higher in resistant hypertension patients when compared to moderate essential hypertension (EH) patients. This difference appears to be independent of clinical blood pressure (BP). Night-time BP appears to be a more accurate predictor of PWV in EH. In another study we demonstrated that primary hyperparathyroidism (PH) (both hypertensive or non-hypertensive forms) might be associated with higher PWV when compared to EH patients or to normotensive controls and that this difference is independent of age and clinical BP. Neither calcium serum level, nor parathyroid hormone has been associated with PWV. Specific treatment by parathyroidectomy (PTX) seems to be beneficial for PWV decrease, which might be mainly determined by improved BP control after surgery. Since PTX indications for asymptomatic forms of PH have been discussed, our data suggest the potential benefit to the extent of subclinical organ damage after surgical treatment in these patients. Similarly, we prooved higher PWV in...
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Metabolic and structural differences in primary aldosteronism and essential hypertension
Šomlóová, Zuzana ; Widimský, Jiří (advisor) ; Mlíková Seidlerová, Jitka (referee) ; Červenka, Luděk (referee)
Hypertension is a major risk factor for cardiovascular (CV) disease, and patients with primary aldosteronism (PA) - the most common endocrine cause of hypertension - have a higher incidence of CV complications. The aim of this study was to evaluate the incidence of metabolic differences and organ complications - kidney, heart and blood vessels damage in patients with essential hypertension (EH), PA and its most common forms - idiopathic hyperaldosteronism (IHA) and aldosterone-producing adenoma (APA). We found a higher incidence of metabolic syndrome and a higher incidence of metabolic abnormalities in IHA compared to APA - higher prevalence of metabolic syndrome, higher levels of triglycerides and lower levels of HDL cholesterol and thereby a higher cardiometabolic risk. Metabolic profile of patients with IHA is similar to EH in contrast to APA. Arterial stiffness was expressed as pulse wave velocity (PWV), in central arteries as carotid-femoral PWV and at peripheral level as femoral-ankle PWV. Patients with PA with comparable levels of blood pressure (BP) have higher stiffness of central elastic and peripheral muscular arteries than patients with EH. The main predictor of impaired peripheral arterial stiffness is the plasma aldosterone level. Patients with IHA have higher central arterial...
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Large artery properties in primary and secondary - endocrine hypertension
Rosa, Ján ; Widimský, Jiří (advisor) ; Mlíková Seidlerová, Jitka (referee) ; Špinar, Jindřich (referee)
Arterial stiffness represented by carotid-femoral pulse wave velocity (PWV) is considered to be an independent cardiovascular risk factor. This study was focused on large artery properties investigation in specific forms of hypertension using applanation tonometer Sphygmocor (Atcor Medical). PWV was significantly higher in resistant hypertension patients when compared to moderate essential hypertension (EH) patients. This difference appears to be independent of clinical blood pressure (BP). Night-time BP appears to be a more accurate predictor of PWV in EH. In another study we demonstrated that primary hyperparathyroidism (PH) (both hypertensive or non-hypertensive forms) might be associated with higher PWV when compared to EH patients or to normotensive controls and that this difference is independent of age and clinical BP. Neither calcium serum level, nor parathyroid hormone has been associated with PWV. Specific treatment by parathyroidectomy (PTX) seems to be beneficial for PWV decrease, which might be mainly determined by improved BP control after surgery. Since PTX indications for asymptomatic forms of PH have been discussed, our data suggest the potential benefit to the extent of subclinical organ damage after surgical treatment in these patients. Similarly, we prooved higher PWV in...
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Interactive Influence of Genetic Effects and Effects of External Environment on Properties of Large Arteries in Relation to Sodium Management
Seidlerová, Jitka ; Filipovský, Jan (advisor) ; Widimský, Jiří (referee) ; Segers, Patrick (referee) ; Herijgers, Paul (referee)
In line with Guyton's work, the goal of our research was to explore in three European populations whether the properties of large arteries are associated with renal sodium handling, which itself changes with environmental factors and with variation in a large number of genes. Before engaging in the genetic analyses proper, we first studied the familial aggregation and the heritability of arterial properties. In all our analyses, we accounted for relatedness among participants and for covariables and confounders. In a first study, we compared the arterial characteristics and blood pressure (BP) in normotensive offspring of two normotensive parents (OFF/NT) and normotensive offspring, who had at least one hypertensive parent (OFF/HT). We measured peripheral pulse pressure (PPp) by conventional and 24-h ambulatory BP. A SphygmoCor device was used to determine the central (CAIx) and peripheral (PAIx) augmentation indexes, central pulse pressure (PPc), and aortic pulse wave velocity (aPWV). Compared with OFF/NT (n=59; 16 to 34 years of age), the OFF/HT (n=174; 17 to 40 years) had higher (0.14<P<0.0007) BP and PPp on conventional measurement (121/75 vs. 114/71 mm Hg and 46 vs. 42 mm Hg) as well as on 24-h ambulatory monitoring (118/70 vs. 114/67 mm Hg and 48 vs. 47 mm Hg). OFF/HT, compared with OFF/NT, also had...
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New types of lead-free solders and their properties
Drápala, J. ; Petlák, D. ; Malcharcziková, J. ; Vodárek, V. ; Konečná, K. ; Smetana, B. ; Zlá, S. ; Kostiuková, G. ; Seidlerová, J. ; Lasek, S. ; Madaj, M. ; Kroupa, Aleš ; Urbánek, J. ; Dušek, K. ; Sedláček, J. ; Sidorov, V.E.
Ternary and binary alloys with different ratios of Ag, Al, Bi, Cu, In, Mg, Sb, Sn and Zn were prepared experimentally. The following characteristics were studied: temperatures and enthalpies of phase transformations (DTA, TG, DSC), macro-and micro-structural analysis, micro-hardness, chemical analysis, X-ray and density measurements and electrical resistivity of selected solders, test of wettability with or without use of fluxes, measurement of corrosion properties.
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