title: The ERK1/2 pathway participates in the upregulation of the expression of mesenteric artery α1 receptors by intravenous tail injections of mmLDL in mice.
abstract: Minimally modified low density lipoprotein (mmLDL) is a risk factor for cardiovascular diseases. However, no studies examining the effect of mmLDL on vascular smooth muscle receptors have been released. The current study investigated the effect of mmLDL on the mesenteric artery α1 adrenoceptor and the molecular mechanisms. Mice were divided into the normal saline (NS), mmLDL, and mmLDL+U0126 groups. In the mmLDL+U0126 group, the animals were subjected to an intravenous tail injection of mmLDL and an intraperitoneal injection of U0126. Vascular tension caused by noradrenaline (NA) in mesenteric arteries was measured with a sensitive myograph system. The serum levels of oxLDL, TNF-α, and IL-1β were detected using enzyme-linked immunosorbent assays. The expressions of the α1 adrenoceptor, the α2 adrenoceptor, TNF-α, IL-1β, and pERK1/2 were detected using real-time polymerase chain reactions and Western blot analysis. Compared with the NS group, the mmLDL group exhibited a noticeably enhanced NA shrinkage dose-response curve and a significantly increased Emax value (P<0.01). Prazosin (α1 adrenoceptor antagonist) caused a noticeable right shift of the dose-response curve. U0126 inhibited the increases in the serum levels and vessel wall expression of IL-1β and TNF-α and enhanced the NA shrinkage dose-response curve caused by mmLDL, as observed by a significantly decreased Emax value (P<0.01). It inhibited the increased α1 adrenoceptor expression caused by mmLDL. The serum levels of IL-1β and TNF-α demonstrated a positive correlation with the NA-induced maximum shrinkage percentage. U0126 inhibited the mmLDL-induced increase in the pERK1/2 protein level in the vessel wall. In conclusion, mmLDL increased the serum levels of IL-1β and TNF-α in vivo by activating the ERK1/2 pathway, which resulted in α1 receptor-mediated vasoconstriction and an increase in the expression of α1 adrenoceptor. The results of this study may provide new ideas for the prevention and cure of cardiovascular diseases in the future.
authors.affiliation: The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, Hu'nan, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, Hu'nan, China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.
authors.forename: Cang-Bao
authors.initials: CB
authors.lastname: Xu
authors.affiliation: Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hu'nan, China.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Jiang
authors.affiliation: The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, Hu'nan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
authors.forename: En-Qi
authors.initials: EQ
authors.lastname: Liu
authors.affiliation: Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hu'nan, China.
authors.forename: Xu-Ping
authors.initials: XP
authors.lastname: Qin
authors.affiliation: The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, Hu'nan, China; Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hu'nan, China. Electronic address: lijieemail2005@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D007275:Injections, Intravenous; D053583:Interleukin-1beta / Q000097:blood; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008813:Mice, Inbred ICR; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D053583:Interleukin-1beta; D008077:Lipoproteins, LDL; D018340:Receptors, Adrenergic, alpha-1; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein
keywords: 5-hydroxytryptamine (PubChem CID: 5202); Acetylcholine (PubChem CID: 6060); Extracellular signal-regulated kinase type 1/2; IL-1β; Mesenteric artery; Minimally modified low density lipoprotein; Noradrenaline (PubChem CID: 439,260); Prazosin (PubChem CID: 68,546); Rauwolscine (PubChem CID: 197,067); TNF-α; U0126 (PubChem CID: 3,006,531); α(1) adrenoceptor