title: Minimally Modified LDL-Induced Impairment of Endothelium-Dependent Relaxation in Small Mesenteric Arteries of Mice.
abstract: Minimally modified low-density lipoprotein (mmLDL) is a well-known risk factor for cardiovascular diseases. The present study was designed to investigate the role of mmLDL in the endothelium-dependent relaxation of mouse mesenteric arteries. A sensitive myograph system was employed to examine the endothelial function of mesenteric arteries. mRNA and protein expression levels were determined using real-time PCR and Western blotting, respectively. The ultramicrostructure of mesenteric vascular beds was investigated using a transmission electron microscope. The results showed that mmLDL significantly impaired the acetylcholine-induced (3 × 10-10 to 1 × 10-4M) endothelium-dependent relaxation of mouse mesenteric arteries with markedly reduced pIC50 (p < 0.05) and Rmax values (p < 0.001). In addition, mmLDL increased the levels of superoxide production and nitrotyrosine concentration and impaired the endothelial microstructure with decreased KCa3.1 and KCa2.3 expression. In conclusion, mmLDL increases superoxide and nitrotyrosine levels, damages endothelial microstructure with decreased KCa3.1 and KCa2.3 expression, and ultimately attenuates relaxation mediated by nitric oxide- and endothelium-derived hyperpolarizing factor.
authors: The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, China.
authors: Gen
authors: G
authors: Chen
authors: Jun-Jie
authors: JJ
authors: Wang
authors: Cang-Bao
authors: CB
authors: Xu
authors: Lei
authors: L
authors: Cao
authors: Jie
authors: J
authors: Lin
authors: Xu-Ping
authors: XP
authors: Qing
authors: Si-Yu
authors: SY
authors: Liu
authors: En-Qi
authors: EQ
authors: Liu
authors: Jie
authors: J
authors: Li
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496925:Kcnn4 protein, mouse; D008077:Lipoproteins, LDL; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; C099252:oxidized low density lipoprotein; D013481:Superoxides; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine