However, importantly when disease was modelled whereby HUVEC were stimulated with TNFα to induce endothelial dysfunction (and a state of inflammation), beta-blockers were able to significantly reduce IL-1b (bisoprolol and metoprolol) and IL-6 (carvedilol, bisoprolol, and metoprolol), but they had no effect on the critical regulator of the inflammasome, NLRP3. Interestingly, in isolated primary HUVECs all three beta-blockers, carvedilol, bisoprolol, and metoprolol increased expression of PTGS2, which encodes cyclooxygenase 2 (COX2), an enzyme largely recognised to be pro-inflammatory. The gene discussed is NLRP3; the disease is endothelial dysfunction.