COX-2-derived prostaglandins in cardiac hypertrophy: Dual roles in injury and repair.

Cardiac hypertrophy represents a primary adaptive response of the heart to both mechanical stress and neurohormonal stimuli. However, beneficial hypertrophic adaptation eventually gives rise to maladaptive structural changes in the heart, ultimately leading to heart failure. Cyclooxygenase-2 (COX-2), a stress-inducible enzyme participating in the metabolism of arachidonic acid-derived eicosanoids, has been recognized as a central modulator of the adaptive changes of the hypertrophic heart through the production of bioactive prostaglandins. However, a growing number of studies have demonstrated the dual roles of COX-2-derived prostaglandins in the context of cardiac hypertrophy. Prostaglandin E₂ (PGE₂) and Prostaglandin I₂ (PGI₂), in addition to Prostaglandin D₂ (PGD₂), have been demonstrated as the major bioactive molecules primarily involved in this biological process. These prostaglandins exert their biological effects through the interaction of G-protein-coupled receptors. While the upregulation of COX-2 in the early injury phase enhances the inflammatory response as well as the release of the mentioned prostaglandins, which in turn primarily contributes to the aggravation of the injury of the heart muscle in the early phase of injury. On the contrary, the re-expression of COX-2 in the later phases primarily contributes to the cardioprotective response of the heart. The dual temporal nature of this process makes it complex. The purpose of this review is to compile the evolving data regarding the emerging dual roles of COX-2-derived prostaglandins in the context of cardiac hypertrophy.