Cardiovascular effects of cyclooxygenase-2 inhibitors: a mechanistic and clinical perspective

Linked ArticlesThis article is part of a joint Themed section with the British Journal of Pharmacology on Targeting Inflammation to Reduce Cardiovascular Disease Risk: a Realistic Clinical Prospect? The rest of the Themed section will appear in a future issue of BJP and will be available at Prostaglandin (PG) H synthase 2 [also referred to colloquially as cyclooxygenase (COX) 2] represents a key enzyme in arachidonic acid metabolism in health and disease. It is both constitutively expressed in several human tissues (e.g. kidney and brain) and induced in various cell types (including monocytes/macrophages, vascular endothelial cells and colorectal cancer cells) in response to inflammatory cytokines, laminar shear stress and growth factors. Products of COX-2 activity (e.g. PGE(2) and prostacyclin) are involved in diverse physiological and pathophysiological processes, including renal haemodynamics and the control of blood pressure, endothelial thromboresistance, pain and inflammation, and colorectal tumorigenesis. Therefore, it is not surprising that COX-2 inhibitors display multifaceted clinical effects, ranging from reduced pain and inflammation to increased blood pressure, an increased risk of atherothrombotic events and a decreased risk of colorectal cancer. The aim of the present article was to review the cardiovascular effects of COX-2 inhibitors [traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) and coxibs alike], with a focus on the mechanisms contributing to the clinical readouts of COX-2 inhibition.