Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul;236(7):4857-4873.
doi: 10.1002/jcp.30235. Epub 2021 Jan 11.

The antithetic role of ceramide and sphingosine-1-phosphate in cardiac dysfunction

Federica Cirillo  1 , Marco Piccoli  1 , Andrea Ghiroldi  1 , Michelle M Monasky  2 , Paola Rota  3 , Paolo La Rocca  4 , Adriana Tarantino  1   2 , Sara D'Imperio  1   2 , Paola Signorelli  5 , Carlo Pappone  2   6 , Luigi Anastasia  1   6
Affiliations
Review

The antithetic role of ceramide and sphingosine-1-phosphate in cardiac dysfunction

Federica Cirillo et al. J Cell Physiol. 2021 Jul.

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death globally and the number of cardiovascular patients, which is estimated to be over 30 million in 2018, represent a challenging issue for the healthcare systems worldwide. Therefore, the identification of novel molecular targets to develop new treatments is an ongoing challenge for the scientific community. In this context, sphingolipids (SLs) have been progressively recognized as potent bioactive compounds that play crucial roles in the modulation of several key biological processes, such as proliferation, differentiation, and apoptosis. Furthermore, SLs involvement in cardiac physiology and pathophysiology attracted much attention, since these molecules could be crucial in the development of CVDs. Among SLs, ceramide and sphingosine-1-phosphate (S1P) represent the most studied bioactive lipid mediators, which are characterized by opposing activities in the regulation of the fate of cardiac cells. In particular, maintaining the balance of the so-called ceramide/S1P rheostat emerged as an important novel therapeutical target to counteract CVDs. Thus, this review aims at critically summarizing the current knowledge about the antithetic roles of ceramide and S1P in cardiomyocytes dysfunctions, highlighting how the modulation of their metabolism through specific molecules, such as myriocin and FTY720, could represent a novel and interesting therapeutic approach to improve the management of CVDs.

Keywords: cardioprotection; cardiovascular diseases; ceramide; sphingolipids; sphingosine 1-phosphate.

PubMed Disclaimer

References

REFERENCES

    1. Allende, M. L., Sasaki, T., Kawai, H., Olivera, A., Mi, Y., van Echten-Deckert, G., Hajdu, R., Rosenbach, M., Keohane, C. A., Mandala, S., Spiegel, S., & Proia, R. L. (2004). Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. Journal of Biological Chemistry, 279(50), 52487-52492. https://doi.org/10.1074/jbc.M406512200
    1. Argaud, L., Prigent, A. F., Chalabreysse, L., Loufouat, J., Lagarde, M., & Ovize, M. (2004). Ceramide in the antiapoptotic effect of ischemic preconditioning. American Journal of Physiology: Heart and Circulatory Physiology, 286(1), H246-H251. https://doi.org/10.1152/ajpheart.00638.2003
    1. Astle, W. J., Elding, H., Jiang, T., Allen, D., Ruklisa, D., Mann, A. L., Mead, D., Bouman, H., Riveros-Mckay, F., Kostadima, M. A., Lambourne, J. J., Sivapalaratnam, S., Downes, K., Kundu, K., Bomba, L., Berentsen, K., Bradley, J. R., Daugherty, L. C., Delaneau, O., … Soranzo, N. (2016). The allelic landscape of human blood cell trait variation and links to common complex disease. Cell, 167(5), 1415-1429.
    1. Bandhuvula, P., Honbo, N., Wang, G. Y., Jin, Z. Q., Fyrst, H., Zhang, M., Borowsky, A. D., Dillard, L., Karliner, J. S., & Saba, J. D. (2011). S1P lyase: A novel therapeutic target for ischemia-reperfusion injury of the heart. American Journal of Physiology: Heart and Circulatory Physiology, 300(5), H1753-H1761. https://doi.org/10.1152/ajpheart.00946.2010
    1. Baranowski, M., Blachnio, A., Zabielski, P., & Gorski, J. (2007). PPARalpha agonist induces the accumulation of ceramide in the heart of rats fed high-fat diet. Journal of Physiology and Pharmacology, 58(1), 57-72.

Publication types

LinkOut - more resources