Transcriptional induction of endothelial nitric oxide synthase type III by lysophosphatidylcholine.
Endothelial synthesis of NO is catalyzed by constitutive NO synthase type III (NOS-III). NOS-III has been thought to be regulated mainly at the level of enzyme activity by intracellular calcium. We report that in human umbilical vein endothelial cells lysophosphatidylcholine (lyso-PC), a component of atherogenic lipoproteins and atherosclerotic lesions, increases NOS-III mRNA and protein levels. This leads to the augmentation of NOS-III activity and the enhancement of antiplatelet properties of endothelial cells. Importantly, nuclear run-off experiments demonstrate a transcriptional mechanism of regulation of NOS-III expression by lysophosphatidylcholine. As endothelium-derived NO appears to be an anti-atherogenic molecule, induction of NOS-III by lyso-PC may be a protective response that limits the progress of the atherosclerotic lesion and promotes its regression.
Zembowicz
A
A
Vascular Biology Research Center, University of Texas Houston Health Science Center 77030, USA.
Tang
J L
JL
Wu
K K
KK
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases