title: Sphingolipid De Novo Biosynthesis: A Rheostat of Cardiovascular Homeostasis.
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.
authors: Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
authors: Linda
authors: L
authors: Sasset
authors: Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
authors: Yi
authors: Y
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Teresa M
authors: TM
authors: Dunn
authors: 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.
authors: Annarita
authors: A
authors: Di Lorenzo
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D000070798:Nogo Proteins / Q000378:metabolism; D013107:Sphingolipids / Q000096:biosynthesis* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D000070798:Nogo Proteins; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Nogo-B; SPT; cardiovascular diseases; sphingolipids