Biomaterial Database

Lactosylceramide causes endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells. 2009

Jean Bismuth, and Hong Chai, and Peter H Lin, and Qizhi Yao, and Changyi Chen

Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.

BACKGROUND Lactosylceramide (LacCer) is a member of the glycosphingolipid family, which has been implicated in the atherogenic process. The goal of this study was to determine the effects and molecular mechanisms of LacCer on endothelial functions in porcine coronary arteries and human coronary endothelial cells (HCAECs). METHODS The vessel rings and HCAECs were treated with different concentrations of LacCer for 24 hours. Vasomotor function was studied using a myograph tension system in response to thromboxane A2 analog U46619, bradykinin and sodium nitroprusside (SNP). Superoxide anion production was determined using lucigenin-enhanced chemiluminescence. The expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase subunit NOX4 and catalase was determined by real-time PCR. RESULTS LacCer (0.1, 1 and 10 microM) significantly decreased endothelium-dependent vasorelaxation (bradykinin) in porcine coronary artery rings in a concentration-dependent manner compared with untreated controls (P<0.05). High concentration of LacCer (10 microM) also reduced endothelium-independent vasorelaxation (SNP). However, LacCer did not affect vessel contraction (U46619). Antioxidant selenomethionine (SeMet) effectively reversed LacCer-induced endothelial dysfunction in the vessel rings. Furthermore, LacCer significantly increased superoxide anion production in the vessel rings in a concentration-dependent manner compared with untreated controls (P<0.05). In response to LacCer treatment, NOX4 mRNA levels were significantly increased, while the expression of catalase and eNOS was significantly decreased in HCAECs compared with controls (P<0.05). CONCLUSIONS LacCer causes endothelial dysfunction with potential mechanisms of the down-regulation of eNOS and increase of oxidative stress due to the activation of NADPH oxidase and inhibition of internal antioxidant catalase. This study suggests that LacCer may represent a risk factor to the vascular system and antioxidant SeMet may have clinical applications for prevention of vascular disease.

UI	MeSH Term	Description	Entries
D007790	Lactosylceramides	Glycosphingolipids which contain as their polar head group a lactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in lactosylceramide beta-galactosidase, is the cause of lactosylceramidosis.	Lactosyl Ceramides,Ceramides, Lactosyl
D008297	Male		Males
D009213	Myography	The recording of muscular movements. The apparatus is called a myograph, the record or tracing, a myogram. (From Stedman, 25th ed)	Myographies
D003331	Coronary Vessels	The veins and arteries of the HEART.	Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074663	NADPH Oxidase 4	An NADPH oxidase that is strongly expressed in the kidney. It forms a complex with CYBA-P22PHOX and produces intracellular SUPEROXIDES that may regulate cellular signaling in APOPTOSIS; BONE RESORPTION; and NF-KAPPA B activation.	Nox4 Protein,Renal NAD(P)H Oxidase,Renox NAD(P)H Oxidase,Oxidase 4, NADPH
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000975	Antioxidants	Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues.	Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D012645	Selenomethionine	Diagnostic aid in pancreas function determination.	Butanoic acid, 2-amino-4-(methylseleno)-,Radioselenomethionine,Selenomethionine Se 75,Selenomethionine Hydrochloride, (S)-Isomer,Selenomethionine, (+,-)-Isomer,Selenomethionine, (R)-Isomer,Selenomethionine, (S)-Isomer,Sethotope,Se 75, Selenomethionine