JMA J. 2026 May 15;9(3):592-601. doi: 10.31662/jmaj.2025-0594. Epub 2026 Mar 19.
ABSTRACT
Sphingolipids are essential components of the cell membrane that can be metabolized into bioactive metabolites such as sphingosine-1-phosphate (S1P), which function as signaling molecules both inside and outside cells. S1P primarily regulates cell survival, proliferation, migration, and adhesion by binding to S1P receptors (S1PRs). Sphingolipid signaling is essential for normal cardiovascular development, with impaired S1P production or defective S1PRs leading to embryonic lethality in mice due to vascular defects. Abnormal activation of sphingolipid signaling in pathologies such as atherosclerosis and pulmonary hypertension leads to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Pharmacological inhibition of the S1PR pathway is clinically available. By outlining current knowledge on sphingolipid signaling in VSMCs and its role in associated vascular diseases, this review intends to highlight the need to advance research targeting VSMCs as a potential therapeutic option for cardiovascular diseases.
PMID:42266796 | PMC:PMC13246252 | DOI:10.31662/jmaj.2025-0594