PMID: 9546652Apr 18, 1998Paper

Atherogenic concentrations of native low-density lipoproteins down-regulate nitric-oxide-synthase mRNA and protein levels in endothelial cells

European Journal of Biochemistry
F VidalLina Badimon

Abstract

The nitric oxide synthase family of proteins is the unique class of mammalian enzymes that metabolizes L-arginine to form nitric oxide (NO). The atherogenic action of low-density lipoproteins (LDL) may be mediated, in part, by its effects on endothelial-derived nitric oxide. To determine whether native LDL (nLDL), at atherogenic concentrations, are capable of modulating NO synthase expression, we treated human umbilical vein endothelial cells with increasing concentrations of human nLDL (0-240 mg cholesterol/dl) for various time periods (2-48 h). Northern and western blot analyses indicate that both endothelial NO-synthase mRNA and protein are down-regulated by atherogenic concentrations of nLDL (180 and 240 mg cholesterol/dl) after 48 h of incubation. Cycloheximide and actinomycin D experiments suggest that this down-regulation operates at a transcriptional level. Additionally, treatment of the cells with high-density lipoproteins, at human physiological concentrations (45 mg cholesterol/dl), does not appear to alter the expression of endothelial NO synthase which seems to indicate that nLDL affect the gene transcription rate by a specific and concentration-dependent mechanism. These findings may have important implications be...Continue Reading

Citations

Feb 24, 2000·The Journal of Pathology·H Li, U Förstermann
Dec 19, 2007·Pharmaceutical Research·R Preston MasonTadeusz Malinski
Oct 24, 2002·Journal of the American College of Cardiology·Claudio NapoliLouis J Ignarro
Oct 17, 2002·Nitric Oxide : Biology and Chemistry·Huige LiUlrich Förstermann
Sep 14, 2012·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Yukihito HigashiKensuke Noma
Jul 10, 2004·Antioxidants & Redox Signaling·Patrizia FerroniGiovanni Davì
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Apr 12, 2011·Thrombosis and Haemostasis·Lina BadimonGemma Vilahur
Oct 2, 2009·Revista española de cardiología·Lina BadimónTeresa Padró
Apr 9, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Matthias Endres
Apr 25, 2008·Pathophysiology : the Official Journal of the International Society for Pathophysiology·M KhazaeiI Laher
May 3, 2012·Annals of the New York Academy of Sciences·Lina Badimon, Gemma Vilahur
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