The role of sphingosine 1‐phosphate and its receptors in cardiovascular diseases

Abstract

There are many different types of cardiovascular diseases, which impose a huge economic burden due to their extremely high mortality rates, so it is necessary to explore the underlying mechanisms to achieve better supportive and curative care outcomes. Sphingosine 1‐phosphate (S1P) is a bioactive lipid mediator with paracrine and autocrine activities that acts through its cell surface S1P receptors (S1PRs) and intracellular signals. In the circulatory system, S1P is indispensable for both normal and disease conditions; however, there are very different views on its diverse roles, and its specific relevance to cardiovascular pathogenesis remains elusive. Here, we review the synthesis, release and functions of S1P, specifically detail the roles of S1P and S1PRs in some common cardiovascular diseases, and then address several controversial points, finally, we focus on the development of S1P‐based therapeutic approaches in cardiovascular diseases, such as the selective S1PR1 modulator amiselimod (MT‐1303) and the non‐selective S1PR1 and S1PR3 agonist fingolimod, which may provide valuable insights into potential therapeutic strategies for cardiovascular diseases.

Screening of sphingolipid metabolism-related genes associated with immune cells in myocardial infarction: a bioinformatics analysis

“…Ceramides are a class of lipids thought to be toxic, and their pathway enzymes are upregulated in ischemic myocardium, which may be one of the sources of plasma ceramide during MI ( 37 ). Furthermore, S1P generated by Asah1 phosphorylation has been shown to inhibit inflammatory neutrophil recruitment and cardiomyocyte apoptosis and may stimulate tissue regeneration and improve cardiac function by attracting hematopoietic stem cells to the infarct site ( 38 ). The release of TNF-a, IL-1b, and IL-6 was significantly reduced in Asah1-overexpressing OBA9 cells ( 39 ).…”

Sphingosine‐1‐phosphate in mitochondrial function and metabolic diseases

“…The S1P axis has antiapoptotic, anti-inflammatory, and vasodilatory characteristics and can sustain the barrier function of endothelial cells, protect cardiomyocyte function, and promote the discharge and activation of lymphocytes, 201,202 these properties are relevant to the development of atherosclerosis, myocardial infarction, heart failure, hypertrophic or fibrotic heart disease, and other illnesses. 203,204 The wide range of S1P signaling can be attributed to the differential expression of S1PR1, S1PR2, S1PR3, S1PR4, and S1PR5 in diverse tissues as well as the plasma transport of via APOM and HDL. [205][206][207] Although the detailed mechanism is yet to be determined, S1P seems to be a new therapeutic target in CVDs.…”

Hypercholesterolemia and Lymphatic Defects: The Chicken or the Egg?

“…In the initial step of its synthesis, ceramidase converts ceramide into sphingosine. Subsequently, sphingosine kinase (Sphk)1 and Sphk2 phosphorylate sphingosine to form S1P ( 43 ). Five subtypes of S1P receptors, including S1PR1- S1PR5, have been reported to be involved in various physiological and pathophysiological events, such as cardiovascular regulation, immune regulation, neurodevelopment, neuroprotection, and fibrogenic responses ( 44 ).…”