Modulation of the reactivity of the vessel wall by local substances derived from the endothelium and perivascular nerves

Weefseldoorbloeding wordt geregeld door een complexe reeks mechanismen die, hoofdzakelijk door het regelen van de diameter van de bloedvaten, zorgen voor het behoud van de weefselhomeostase. Vasodilatatie speelt een belangrijke rol in de regeling van de doorbloeding van een bepaald vaatbed. Het voornaamste doel van het onderzoek verricht in het kader van deze thesis, was meer te weten te komen over het belang en de werkingsmechanismen van verschillende vasodilaterende stoffen (EDHF, cannabinoïden, ...) in geïsoleerde maag- en mesenterische arteriën van de rat om zo tot een beter inzicht te komen over hun rol in de gastro-intestinale doorbloeding. In dit onderzoek werd gebruik gemaakt van verschillende in vitro technieken op geïsoleerde bloedvaten: membraanpotentiaal metingen met behulp van conventionele micro-elektroden, isometrische tensiemetingen met een draadmyograaf en calcium bepalingen door middel van confocale microscopie

Low power all-digital radio-over-fiber transmission for 28-GHz band using parallel electro-absorption modulators

We present a low-power all-digital radio-over-fiber transmitter for beyond 28-GHz using sigma-delta modulation, a 140mW NRZ driver and parallel electro-absorption modulators. 5.25Gb/s (2.625Gb/s) 64-QAM is transported over 10-km SSMF at 1560nm with 7.6% (5.2%) EVM

A008 Presence of tissue factor and other components of atherosclerosis in human aortic valve stenosis

BackgroundIt is now generally accepted that calcific aortic valve disease is an atherosclerotic-like process. Recent studies in an experimental model of aortic valve sclerosis demonstrated the presence of tissue factor (TF), the main contributor to atherosclerotic plaque thrombogenicity, in diseased valve leaflets. We assessed the hypothesis that human aortic valve disease is an atherosclerotic-like process in which TF plays an important role and evaluated the valvular expression and localization of TF and other components of atherosclerosis.MethodsCalcified aortic valves (n=52) were obtained from patients undergoing aortic valve replacement. Leaflet structure, cellular and lipid infiltration and expression of TF, its inhibitors, VEGF and other components of atherosclerosis were evaluated by histological and immunohistochemical staining. TF, TFPI, osteopontin, MMP- 9, TIMP-1 and VEGF antigen were measured by ELISA and TF and alkaline phosphatase activity were determined using chromogenic assays. Finally, we performed semi-quantification of TF transcripts by RT- PCR and further analyzed protein expression by Western blot.ResultsHistological and immunohistochemical staining of the valve leaflets revealed neovascularisation at the centre of the lesions, overall macrophage and myofibroblast infiltration and the abundant presence of MMP-9. On the other hand, TF and TFPI were associated with calcification and extracellular lipid deposits in the fibrosa and the subendothelial layer of the aortic side of the leaflets. Correspondingly, TF antigen and activity were found to be higher in calcified regions of the valve leaflets (733.29±70.49pg/mgvs 429.40±73.17pg/mg and 144.75±14.65pg/mgvs 40.15±6.19pg/mg respectively (p<0.0001)). Similar results were found for osteopontin, MMP-9, TIMP-1 and VEGF. In contrast, TFPI antigen was found to be much lower in these calcified regions (722.54±153.92pg/mgvs 2459.28±285.36pg/mg (p<0.0001)).ConclusionThese results demonstrate that aortic valve lesions display several characteristics of atherosclerosis, including TF expression. In addition, we showed that TF is colocalized with calcification and lipid deposition. Further studies are now set up to evaluate the role of TF in aortic valve disease and its association with other components of the atherosclerotic process

Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1

Local host response following an intramammary challenge with Staphylococcus fleurettii and different strains of Staphylococcus chromogenes in dairy heifers

Coagulase-negative staphylococci (CNS) are a common cause of subclinical mastitis in dairy cattle. The CNS inhabit various ecological habitats, ranging between the environment and the host. In order to obtain a better insight into the host response, an experimental infection was carried out in eight healthy heifers in mid-lactation with three different CNS strains: a Staphylococcus fleurettii strain originating from sawdust bedding, an intramammary Staphylococcus chromogenes strain originating from a persistent intramammary infection (S. chromogenes IM) and a S. chromogenes strain isolated from a heifer's teat apex (S. chromogenes TA). Each heifer was inoculated in the mammary gland with 1.0 x 10(6) colony forming units of each bacterial strain (one strain per udder quarter), whereas the remaining quarter was infused with phosphate-buffered saline. Overall, the CNS evoked a mild local host response. The somatic cell count increased in all S. fleurettii-inoculated quarters, although the strain was eliminated within 12 h. The two S. chromogenes strains were shed in larger numbers for a longer period. Bacterial and somatic cell counts, as well as neutrophil responses, were higher after inoculation with S. chromogenes IM than with S. chromogenes TA. In conclusion, these results suggest that S. chromogenes might be better adapted to the mammary gland than S. fleurettii. Furthermore, not all S. chromogenes strains induce the same local host response

Does Diabetes Accelerate the Progression of Aortic Stenosis through Enhanced Inflammatory Response within Aortic valves?

Diabetes predisposes to aortic stenosis (AS). We aimed to investigate if diabetes affects the expression of selected coagulation proteins and inflammatory markers in AS valves. Twenty patients with severe AS and concomitant type 2 diabetes mellitus (DM) and 40 well-matched patients without DM scheduled for valve replacement were recruited. Valvular tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, C-reactive protein (CRP) expression were evaluated by immunostaining and TF, prothrombin, and CRP transcripts were analyzed by real-time PCR. DM patients had elevated plasma CRP (9.2 [0.74–51.9] mg/l vs. 4.7 [0.59–23.14] mg/l, p = 0.009) and TF (293.06 [192.32–386.12] pg/ml vs. 140 [104.17–177.76] pg/ml, p = 0.003) compared to non-DM patients. In DM group, TF−, TFPI−, and prothrombin expression within valves was not related to demographics, body mass index, and concomitant diseases, whereas increased expression related to DM was found for CRP on both protein (2.87 [0.5–9]% vs. 0.94 [0–4]%, p = 0.01) and transcript levels (1.3 ± 0.61 vs. 0.22 ± 0.43, p = 0.009). CRP-positive areas were positively correlated with mRNA TF (r = 0.84, p = 0.036). Diabetes mellitus is associated with enhanced inflammation within AS valves, measured by CRP expression, which may contribute to faster AS progression