Glycerophospholipid and Sphingosine- 1-phosphate Metabolism in Cardiovascular Disease: Mechanisms and Therapeutic Potential.

Abstract

Cardiovascular disease remains a leading cause of mortality worldwide, driven by factors such as dysregulated lipid metabolism, oxidative stress, and inflammation. Recent studies highlight the critical roles of both glycerophospholipid and sphingosine- 1-phosphate metabolism in the pathogenesis of cardiovascular disorders. However, the contributions of glycerophospholipid-derived metabolites remain underappreciated. Glycerophospholipid metabolism generates bioactive molecules that contribute to endothelial dysfunction, lipid accumulation, and cardiac cell injury while also modulating inflammatory and oxidative stress responses. Meanwhile, sphingosine- 1-phosphate is a bioactive lipid mediator that regulates vascular integrity, inflammation, and cardiac remodeling through its G-protein-coupled receptors. The convergence of these pathways presents novel therapeutic opportunities, where dietary interventions such as omega- 3 polyunsaturated fatty acids and pharmacological targeting of sphingosine- 1-phosphate receptors could synergistically mitigate cardiovascular risk. This review underscores the need for further investigation into the interplay between glycerophospholipid metabolism and sphingosine- 1-phosphate signaling to advance targeted therapies for the prevention and management of cardiovascular disease.