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Trends Endocrinol Metab. 2016 Nov;27(11):807-819. doi: 10.1016/j.tem.2016.07.005. Epub 2016 Aug 22.

Sphingolipid De Novo Biosynthesis: A Rheostat of Cardiovascular Homeostasis.

Author information

1
Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
2
Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
3
Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA. Electronic address: and2039@med.cornell.edu.

Abstract

Sphingolipids (SL) are both fundamental structural components of the eukaryotic membranes and signaling molecules that regulate a variety of biological functions. The highly-bioactive lipids, ceramide and sphingosine-1-phosphate, have emerged as important regulators of cardiovascular function in health and disease. In this review we discuss recent insights into the role of SLs, particularly ceramide and sphingosine-1-phosphate, in the pathophysiology of the cardiovascular system. We also highlight advances into the molecular mechanisms regulating serine palmitoyltransferase, the first and rate-limiting enzyme of de novo SL biosynthesis, with an emphasis on the recently discovered inhibitors of serine palmitoyltransferase, ORMDL and NOGO-B proteins. Understanding the molecular mechanisms regulating this biosynthetic pathway may lead to the development of novel therapeutic approaches for the treatment of cardiovascular diseases.

KEYWORDS:

Nogo-B; SPT; cardiovascular diseases; sphingolipids

PMID:
27562337
PMCID:
PMC5075255
DOI:
10.1016/j.tem.2016.07.005
[Indexed for MEDLINE]
Free PMC Article

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