title: Minimally modified LDL upregulates endothelin type B receptors in rat basilar artery.
abstract: Minimally modified low density lipoprotein (mmLDL) is a well-known risk factor for cerebral vascular diseases and upregulation of endothelin type B (ET(B)) receptors plays key roles in the pathogenesis. The present study was designed to examine if mmLDL upregulated endothelin ET(B) receptors in basilar artery and its possible intracellular signaling molecular mechanisms. Rat basilar arteries were cultured for 24h in the presence of mmLDL with specific inhibitors. The artery contractile responses and receptor expressions of mRNA and protein were investigated using myograph system, real-time PCR and Western blot techniques, respectively. Results showed that ET(B) receptor agonist, sarafotoxin 6c induced a weak contraction in fresh basilar artery segments. After organ culture the contraction curve mediated by ET(B) receptor was shifted towards the left with an increased E(max) of 88 ± 6%. The mmLDL 10 μg/mL further shifted the concentration-contractile curves towards the left with an increased E(max) of 116 ± 12%. The organ culture significantly increased ET(B) receptor mRNA and protein levels from fresh arteries, which was further enhanced by mmLDL. The staurosporine (PKC inhibitor), both SB386023 and U0126 (extracellular signal related kinases 1 and 2 inhibitor), and wedelolactone (NF-κB inhibitor) almost totally abolished organ culture-increased and mmLDL-increased contraction and expressions of endothelin ET(B) receptor. SP600125 (C-jun terminal kinase inhibitor) and SB203580 (p38 inhibitor) attenuated both organ cultured-induced and mmLDL-induced upregulation of endothelin ET(B) receptors. In conclusion, mmLDL upregulates ET(B) receptors of cerebral basilar artery via the PKC, MAPK and NF-κB signal pathways.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Cang-Bao
authors.initials: CB
authors.lastname: Xu
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009213:Myography; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D044023:Receptor, Endothelin B / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D046509:Tissue Culture Techniques; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D014662:Vasoconstrictor Agents; C099252:oxidized low density lipoprotein; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases