BACKGROUND: Patients who underwent surgery for aortic coarctation (COA) have an increased risk of arterial hypertension. We aimed at evaluating (1) differences between hypertensive and non-hypertensive patients and (2) the value of cardiopulmonary exercise testing (CPET) to predict the development or progression of hypertension. METHODS: Between 1999 and 2010, CPET was performed in 223 COA-patients of whom 122 had resting blood pressures of <140/90 mmHg without medication, and 101 were considered hypertensive. Comparative statistics were performed. Cox regression analysis was used to assess the relation between demographic, clinical and exercise variables and the development/progression of hypertension. RESULTS: At baseline, hypertensive patients were older (p=0.007), were more often male (p=0.004) and had repair at later age (p=0.008) when compared to normotensive patients. After 3.6 ± 1.2 years, 29/120 (25%) normotensive patients developed hypertension. In normotensives, VE/VCO2-slope (p=0.0016) and peak systolic blood pressure (SBP; p=0.049) were significantly related to the development of hypertension during follow-up. Cut-off points related to higher risk for hypertension, based on best sensitivity and specificity, were defined as VE/VCO2-slope ≥ 27 and peak SBP ≥ 220 mmHg. In the hypertensive group, antihypertensive medication was started/extended in 48/101 (48%) patients. Only age was associated with the need to start/extend antihypertensive therapy in this group (p=0.042). CONCLUSIONS: Higher VE/VCO2-slope and higher peak SBP are risk factors for the development of hypertension in adults with COA. Cardiopulmonary exercise testing may guide clinical decision making regarding close blood pressure control and preventive lifestyle recommendations.
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Endothelial cells were isolated from arteries and veins obtained from elderly people at autopsy and propagated for 37 to 69 population doublings. The cells secreted tissue-type plasminogen activator (t-PA) and PA inhibitor-1, and, after subculturing, urokinase-type PA (u-PA) antigen. The following differences between endothelial cells from adult arteries and veins were observed: 1) The cells had the potential to be propagated as a healthy monolayer. The diameter of aortic endothelial cells increased after 8 to 19 population doublings, while a homogeneous population of small diameter vena cava cells was retained for 35 population doublings. 2) The amount of secreted t-PA varied. Vena cava cells produced four times more t-PA than aorta cells, and 20-fold more than umbilical artery or vein endothelial cells. The t-PA mRNA content of vena cava cells did not exceed that of aorta cells, but was fourfold greater than that of umbilical cord endothelial cells. 3) The release of u-PA antigen varied. No u-PA antigen was detectable in conditioned medium of primary cultures of human aorta and vena cava endothelial cells or of early passage vena cava cells. After prolonged subculturing, vena cava cells started to secrete u-PA. Endothelial cells from aorta and other adult arteries, however, started secreting u-PA after one to four passages, parallel to the occurrence of enlarged endothelial cells. u-PA was present as a u-PA/inhibitor complex and as a single-chain u-PA. These differences may be developmentally related to their artery or vein origin or may reflect differences acquired during the "life history" of these blood vessels in vivo. Our data suggest that the release of u-PA antigen by human macrovascular endothelial cells can be used as an indicator of cell senescence.
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Klotho knock-out mice are an important model for vascular calcification, which is associated with chronic kidney disease. In chronic kidney disease, serum magnesium inversely correlates with vascular calcification. Here we determine the effects of serum magnesium on aortic calcification in Klotho knock-out mice treated with a minimal or a high magnesium diet from birth. After eight weeks, serum biochemistry and aorta and bone tissues were studied. Protective effects of magnesium were characterized by RNA-sequencing of the aorta and micro-CT analysis was performed to study bone integrity. A high magnesium diet prevented vascular calcification and aortic gene expression of Runx2 and matrix Gla protein found in such mice on the minimal magnesium diet. Differential expression of inflammation and extracellular matrix remodeling genes accompanied the beneficial effects of magnesium on calcification. High dietary magnesium did not affect serum parathyroid hormone, 1,25-dihydroxyvitamin D3 or calcium. High magnesium intake prevented vascular calcification despite increased fibroblast growth factor-23 and phosphate concentration in the knock-out mice. Compared to mice on the minimal magnesium diet, the high magnesium diet reduced femoral bone mineral density by 20% and caused excessive osteoid formation indicating osteomalacia. Osteoclast activity was unaffected by the high magnesium diet. In Saos-2 osteoblasts, magnesium supplementation reduced mineralization independent of osteoblast function. Thus, high dietary magnesium prevents calcification in Klotho knock-out mice. These effects are potentially mediated by reduction of inflammatory and extracellular matrix remodeling pathways within the aorta. Hence magnesium treatment may be promising to prevent vascular calcification, but the risk for osteomalacia should be considered.
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Criminelen maken voor georganiseerde criminaliteit gebruik van legale bedrijven en diensten. Door deze vermenging van illegale en legale economieën vervagen normen en neemt het gevoel van veiligheid en leefbaarheid in de samenleving af. Dit effect wordt ondermijning genoemd. Kenmerkend voor deze illegale activiteiten is dat deze ‘winstgedreven’ zijn. Geldstromen vormen de aorta van de georganiseerde criminaliteit. De hogescholen Avans en Saxion werken samen aan het weerbaar maken van de samenleving tegen de ondermijnende effecten van deze criminele geldstromen. We zien het als onze missie om op deze manier een essentiële bijdrage te leveren aan de aanpak van ondermijnende criminaliteit. Hoewel de aanpak van criminele geldstromen hoog op de agenda staat van belangrijke publieke en private stakeholders, is praktijkgericht onderzoek op dit terrein nog onvoldoende krachtig gebundeld. Het doel van de SPRONG-groep Ondermijning – Criminele Geldstromen (SPOC) is om een landelijk opererend Kennis- en expertisecentrum Criminele Geldstromen op te richten. Onze multidisciplinaire teams werken al lange tijd samen om het onderzoek naar criminele geldstromen en ondermijning een impuls te geven. Dit doen we met onze consortiumpartners in landelijke en regionale netwerken. In de komende vier jaar ligt het accent op infrastructuurontwikkeling. We beginnen deze samenwerking met onze landelijke consortiumpartners, maar geleidelijk zal de focus verschuiven naar de verschillende regio’s. Verder bestaat het activiteitenplan van dit consortium onder meer uit het vaststellen van een roadmap, het aanscherpen van de vraagarticulatie en het verder uitbouwen en bestendigen van onze netwerkinteracties. Daarnaast besteden we veel aandacht aan (interne en externe) talentontwikkeling en dragen we zorg voor disseminatie en nieuwe interacties tussen onderzoek en onderwijs. Binnen dit project willen de samenwerkende lectoren de kans benutten om nieuwe topspecialisten (programmamanager, community managers, alliantiemakelaars, datastewards) aan te trekken voor het maken van nieuwe infrastructuren.
