Cyclooxygenase-2 plays a crucial role during myocardial patterning of developing chick

Cyclooxygenase-2 (COX-2), a member of the Cyclooxygenase family, initiates the biosynthesis of prostanoids that regulates various cellular functions. Our pilot attempt revealed that administration of etoricoxib, an inhibitor specific for COX-2, induces abnormal looping in the chicken heart. The present study attempts to reveal the mechanistic details of etoricoxibinduced abnormal cardiac looping. The activity of COX-2 was inhibited by administering 3.5 μg of etoricoxib into the air cell of the egg on day zero of incubation. The gene and protein expression patterns of the major mediators of heart development were then analyzed on day 2 (HH12) and day 3 (HH20). Reduction in the COX-2 activity deranged the expressions of upstream regulators of organogenesis like Wnt11, BMP4 and SHH in the embryos exposed to etoricoxib. The observed expression shifts in the downstream regulators of myocardial patterning (MYOCD, HAND2, GATA4, GATA5 and GATA6) in the treated embryos corroborate the above results. In addition, the reduction in COX-2 activity hampered the cardiomyocyte proliferation with a concomitant increase in the rate of apoptosis. In conclusion, the collective effect of altered expression of signaling molecules of myocardial patterning and compromised cardiomyocyte turnover rate could be the reason behind the looping defects observed in the heart of etoricoxib-treated chick embryos.