Role of Cyclooxygenase Pathway and Risk Associated with Non-Steroidal Anti-inflammatory Drugs Therapy in Cardiovascular Diseases

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the cyclooxygenase enzyme activity through different
mechanisms and prevent inflammation. But they all have different risks associated with them. Some are associated with
gastrointestinal bleeding and some are strongly allied with the cardiovascular risks. Cyclooxygenase enzyme regulates
prostaglandin synthesis by converting arachidonic acid present at the sn-2 position of membrane phospholipids to
prostaglandin H2. Prostaglandin H2 is the precursor of all prostaglandins. There are two isoforms of cyclooxygenase
enzyme, cyclooxygenase-1 and cyclooxygenase-2 which differ in their active site due to an isoleucine to valine
substitution at amino acid 523 in cyclooxygenase-2. Cyclooxygenase-1 is constitutively expressed in platelets
where it helps in the formation of thromboxane whereas cyclooxygenase-2 is inductive form and is expressed in
the endothelial cells due to shear stress and forms prostacyclins. Both thromboxanes and prostacyclins maintain
the homeostasis of the vascular wall. During vascular injury prostacyclin production decreases as a result of which
thromboxane synthesis increases in the platelets which leads to platelet aggregation. Although, being strongly
associated with cardiovascular risks, NSAIDs are still prescribed to the patients to prevent pain according to their
condition. So this review aims to summarise the mechanism of cyclooxygenase pathway, possible mechanism of
action of NSAIDs and the risks of cardiovascular events associated with the use of NSAIDs.