Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells

AbstractThe prothrombotic mediator thromboxane A2 is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels of different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy

The swimming kinematics of larval Atlantic cod, Gadus morhua L., are resilient to elevated seawater pCO2

Kinematics of swimming behavior of larval Atlantic cod, aged 12 and 27 days post-hatch (dph) and cultured under three pCO2 conditions (control-370, medium-1800, and high-4200 μatm) from March to May 2010, were extracted from swim path recordings obtained using silhouette video photography. The swim paths were analyzed for swim duration, distance and speed, stop duration, and horizontal and vertical turn angles to determine whether elevated seawater pCO2—at beyond near-future ocean acidification levels—affects the swimming kinematics of Atlantic cod larvae. There were no significant differences in most of the variables tested: the swimming kinematics of Atlantic cod larvae at 12 and 27 dph were highly resilient to extremely elevated pCO2 levels. Nonetheless, cod larvae cultured at the highest pCO2 concentration displayed vertical turn angles that were more restricted (median turn angle, 15°) than larvae in the control (19°) and medium (19°) treatments at 12 dph (but not at 27 dph). Significant reduction in the stop duration of cod larvae from the high treatment (median stop duration, 0.28 s) was also observed compared to the larvae from the control group (0.32 s) at 27 dph (but not at 12 dph). The functional and ecological significance of these subtle differences are unclear and, therefore, require further investigation in order to determine whether they are ecologically relevant or spurious

Foraging behaviour of larval cod (Gadus morhua) at low light intensities

The ability to forage at low light intensities can be of great importance for the survival of fish larvae in a pelagic environment. Three-dimensional silhouette imaging was used to observe larval cod foraging and swimming behaviour at three light intensities (dusk ~1.36 × 10ˉ³ W/m², night ~1.38 × 10ˉ4 W/m² and darkness ~3.67 × 10ˉ6 W/m²) at 4 different ages from 6 to 53 days post-hatch (dph). At 6 dph, active pursuit of prey was only observed under dusk conditions. Attacks, and frequent orientations, were observed from 26 dph under night conditions. This was consistent with swimming behaviour which suggested that turn angles were the same under dusk and night conditions, but lower in darkness. Cod at 53 dph attacked prey in darkness and turn angles were not different from those under other light conditions. This suggests that larvae are still able to feed at light intensities of 3.67 × 10ˉ6 W/m². We conclude that larval cod can maintain foraging behaviour under light intensities that correspond to night-time at depths at which they are observed in the field, at least if they encounter high-density patches of prey such as those that they would encounter at thin layers or fronts