31 August 2009
Lactosylceramide causes endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cellsJean BismuthABCDEF, Hong ChaiABCD, Peter H. LinAG, Qizhi YaoABCD, Changyi ChenABCDEFG
Med Sci Monit 2009; 15(9): BR270-274 :: ID: 878174
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).
Material and Method
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.
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).
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.
Keywords: Superoxides - metabolism, Selenomethionine - metabolism, Nitric Oxide Synthase Type III - metabolism, NADPH Oxidase - metabolism, Myography, Lactosylceramides - pharmacology, Endothelium, Vascular - physiology, Endothelial Cells - physiology, Coronary Vessels - physiology, Antioxidants - metabolism, Sus scrofa, Vascular Diseases - physiopathology, Vasodilation - drug effects
01 May 2023 : EditorialEditorial: Twenty Years On from Sequencing the Human Genome, Personalized/Precision Oncology Prepares to Meet the Challenges of Checkpoint Inhibitor Therapy
Med Sci Monit 2023; 29:e940911
28 May 2023 : Database AnalysisScientometric and Visualized Analysis of Intravoxel Incoherent Motion Magnetic Resonance Imaging: 1988-2021
Med Sci Monit In Press; DOI: 10.12659/MSM.938715
25 May 2023 : Database AnalysisThe COVID-19 Crisis and the Incidence of Alcohol-Related Deaths in Poland
Med Sci Monit In Press; DOI: 10.12659/MSM.940904
25 May 2023 : Review articleA Review of Preclinical and Clinical Studies in Support of the Role of Non-Steroidal Anti-Inflammatory Drug...
Med Sci Monit In Press; DOI: 10.12659/MSM.940635
25 May 2023 : Clinical ResearchPeriapical Lesions and Missed Canals in Endodontically Treated Teeth: A Cone-Beam Computed Tomographic Stud...
Med Sci Monit In Press; DOI: 10.12659/MSM.940533
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
01 Jan 2022 : EditorialEditorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...
Med Sci Monit 2022; 28:e935952